There are 4 articles provided only 2 are needed and it only has to be one paragraph. And it also has to go throught turn it in. So please no plagerism.
On the discussion board, using a minimum of two articles that are supporting your PICOT question, submit one paragraph synthesizing the research into clear, concise statements
reviewing each of the studies in the paragraph—but by paraphrasing and synthesizing the work that was done.
PICOT: In type-2 diabetic patient, how does the ketogenic diet compare to a low-calorie diet in the maintenance of weight loss in a one-year time frame?
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Coments from the teacher:
Wow! This weeks assignment was evidently one that no-one understood. May I suggest you go back and at least read the lectures posted on week 6! This lecture stated:
To synthesize is to combine two or more elements to form a new whole. In the literature review, the “elements” are the findings of the literature you gather and read; the “new whole” is the conclusion you draw from those findings.
“Rigorous methods of quantitative assessment are necessary to establish interventions that are both effective and cost-effective. Usually a single study will not fully address these issues and it is desirable to synthesize evidence from multiple sources.
At this point in the process you should aim for synthesis of the material. Synthesizing means comparing different material and highlighting similarities, differences, and connections. When a writer synthesizes successfully, he or she presents new ideas based on interpretations of other evidence or arguments. Critical reading and critical thinking are key components of successful synthesizing.’
Please look at your paragraph and see if you did this (hint: most of you did not!)
There are 4 articles provided only 2 are needed and it only has to be one paragraph. And it also has to go throught turn it in. So please no plagerism. On the discussion board, using a minimum of two
Original Research Effects on Diabetes Medications, Weight and Glycated Hemoglobin Among Adult Patients With Obesity and Type 2 Diabetes: 6-Month Observations From a Full Meal Replacement, Low-Calorie Diet Weight Management Program Judy Y. Shiau MDCM, FRCPC, DipABOM a,*,Derek Y.F. So MD, FRCPC, FACC b, Robert R. Dent MDCM, FRCPC c aLEAF Weight Management Clinic, Division of Endocrinology and Metabolism, University of Ottawa, Ottawa, Ontario, CanadabDivision of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, CanadacWeight Management Clinic, Ottawa Hospital, Division of Endocrinology and Metabolism, University of Ottawa, Ottawa, Ontario, Canada Key Messages •Patients with obesity and diabetes may require intensive strategies for weight management to overcome the barrier of weight- gaining diabetes medications. •A full meal replacement, low-calorie diet in a 6-month weight management program can achieve up to 18.6% weight loss in patients with diabetes. •Within this full meal replacement, low-calorie diet program, medications for diabetes can be signiﬁcantly reduced while con- comitantly achieving good glycemic control. article info Article history:Received 24 January 2017 Received in revised form 12 March 2017 Accepted 15 March 2017 Keywords: diabetes low-calorie diet meal replacement medication changes weight loss abstract Objectives:A 6-month weight-management program with full meal replacement, low-calorie diet (full MR-LCD) (900 kcal/day for 6 to 12 weeks) follows a protocol for patients with diabetes for decreasing or discontinuing weight-gaining diabetes medications ﬁrst (Group WG) and then titrating weight-neutral medications (Group WN). Methods:This is a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes who were taking medications. Results:Group WG and Group WN were similar at baseline, except that glycated hemoglobin (A1C) levels were signiﬁcantly lower in Group WN (7.5% vs. 6.6%; p<0.001). At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92.1% sulfonureas, 86.5% insulins, 78.8% thiazolidinediones, 77.8% alpha-glucosidase inhibitors, 50% meglitinides, 33.3% dipeptidyl peptidase-4 (DPP-4) inhibitors and 32.8% metformin. At 6 months, compared with baseline, A1C levels improved in Group WG and Group WN (6-month A1C levels 6.7% and 5.8%, respectively; p<0.0001), and Group WN had signiﬁcantly better A1C levels than Group WG. At 6 months, 30% of patients were no longer taking diabetes medications and had signiﬁcantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002); both groups had improved glycemic control at 6 months (A1C 6.0% vs. A1C 6.6%; NS). Conclusions:In patients with obesity and type 2 diabetes taking medications, a full MR-LCD program appears to be safe and includes improvement in A1C levels. At 6 months, the percentage of weight loss can be signiﬁcantly better in patients who no longer require diabetes medications, and A1C levels are best con- trolled in patients who are on WN medications. © 2017 Canadian Diabetes Association. * Address for correspondence: Judy Shiau, MDCM, FRCPC, DipABOM, LEAF Weight Management Clinic, 1980 Ogilvie Road, Unit 216, Ottawa, Ontario K1J 9L3,Canada. E-mail address: [email protected] Can J Diabetes 42 (2018) 56–60 Contents lists available at ScienceDirect Canadian Journal of Diabetes journal homepage: www.canadianjournalofdiabetes.com 1499-2671 © 2017 Canadian Diabetes Association. The Canadian Diabetes Association is the registered owner of the name Diabetes Canada. https://doi.org/10.1016/j.jcjd.2017.03.006 Mots clés : diabète régime hypocalorique substitut de repas changements de médicaments perte de poids résumé Objectifs :Un programme de prise en charge du poids d’une durée de 6 mois par une substitution complète des repas-régimes hypocaloriques (SR complète-RH) (900 kcal/jour durant6à12semaines) utilise un protocole destiné aux patients diabétiques pour diminuer ou interrompre les antidiabétiques qui entraînent la prise de poids (groupe PP) et ensuite ajuster la dose des médicaments qui sont sans effet sur le poids (groupe SEP). Méthodes :Il s’agit d’une étude de cohorte rétrospective (de 1992 à 2009) sur le poids, la régulation de la glycémie et les changements d’antidiabétiques chez 317 patients souffrant d’obésité et de diabète de type 2 qui prenaient des médicaments. Résultats :Au début, le groupe PP et le groupe SEP avaient des caractéristiques similaires, à l’exception de l’hémoglobine glyquée (A1c) qui était signiﬁcativement inférieure dans le groupe SEP (7,5 %vs6,6 %; p<0,001). Après 6 mois, les deux groupes avaient perdu 16 % de leur poids; la diminution ou l’interruption des médicaments étaient de 92,1 % pour les sulfonylurées, 86,5 % pour l’insuline, 78,8 % pour les thiazolidinediones, 77,8 % pour les inhibiteurs des alpha-glucosidases, 50 % pour les méglitinides, 33,3 % pour les inhibiteurs de la dipeptidyl peptidase-4 (DPP-4) et 32,8 % pour la metformine. Comparativement au début, les concentrations d’A1c après 6 mois s’amélioraient dans le groupe PP et dans le groupe SEP (des concentrations respectives de l’A1c après 6 mois de 6,7 % et de 5,8 %; p<0,0001), quoique le groupe SEP avait des concentrations d’A1c signiﬁcativement meilleures que le groupe PP. Après 6 mois, 30 % des patients ne prenaient plus d’antidiabétiques et montraient un pourcentage de perte de poids signiﬁcativement meilleur que ceux qui prenaient des médicaments (18,6 %vs16 %; p=0,002); la régulation de la glycémie s’était améliorée chez les deux groupes après 6 mois (A1c de 6,0 %vsA1c de 6,6 %; NS). Conclusions :Chez les patients souffrant d’obésité et de diabète de type 2 qui prennent des médicaments, un programme de SR complète-RH semble démontrer son innocuité et apporte l’amélioration des con- centrations de l’A1c. Après 6 mois, le pourcentage de perte de poids peut être signiﬁcativement meilleur chez les patients qui n’ont plus besoin d’antidiabétiques, alors que les concentrations d’A1c sont mieux maîtrisées chez les patients qui prennent des médicaments SEP. © 2017 Canadian Diabetes Association. Introduction Obesity and diabetes are strongly associated. Both are chronic diseases that are progressive and diﬃcult to treat. Overweight and obesity constitute an estimated 80% to 90% of persons with type 2 diabetes (1) and, in type 1 diabetes, there has been a 7-fold increase in obesity over 20 years (2) . Treatment of obesity in patients with diabetes is further complicated by the fact that some glucose- lowering medications, such as insulin, are associated with weight gain (3,4) . Conversely, weight loss improves glycemic control by increasing insulin sensitivity and glucose uptake and reducing hepatic glucose output (4) . Accordingly, achieving normoglycemia in patients with diabe- tes requires a balance of both weight management and selection of appropriate diabetes medications. In general, the principle of weight reduction is to follow a lower caloric diet that is sustain- able (5) . In patients with type 2 diabetes, hypoglycemic agents that involve the potential for weight gain may reduce the rate of weight loss (6) . Therefore, for management of weight in patients with type 2 diabetes, a balance must be established between sustainable diets and the use of medications for glycemic control. Meal replacements (MRs) show strong evidence as being a good tool for weight management (7) . MRs have been reported in patients with type 2 diabetes and have been shown to produce superior weight loss compared to individualized diet plans. This was observed irrespective of whether it was a partial MR, in which 1 or 2 meals and snacks are replaced by MRs, aiming for a 500 to 1000 daily kcal deﬁcit (8–10) , or full MRs, in which all meals are replaced with MRs as low-calorie diets (LCDs), deﬁned as 800 kcals per day or more. The relationship between changes in hypoglycemic medications and weight loss with full MRs have been described previously in a few small cohorts of 8 to 32 patients (11–13) . The limitations of these studies include the small sample sizes, the narrow choices of hypo- glycemic agents and the severity of the diets which, in 1 study, was 425 kcals per day. The aim of our study was to determine the ben- eﬁcial effects and changes in hypoglycemic agents within a behavioural program using full MR-LCDs in patients with obesity and diabetes. We hypothesized that in a full MR, medicallysupervised weight-management program, patients with diabetes would lose weight, require less hypoglycemic medications and have improved glycemic control. Methods A retrospective cohort study was conducted in 2744 patients con- secutively enrolled between 1992 and 2009 in the CORE program at the Ottawa Hospital Weight Management Clinic (OHWMC) in Ontario, Canada. The study protocol was approved by The Ottawa Hospital Research Ethics Board. The CORE program enrols patients with diagnosed obesity so as to assist in weight management, with the goal of improving long-term health. The CORE program is a year- long, comprehensive, intensive lifestyle behavioural program. Intervention The ﬁrst 6 months (week 1 to week 26) include mandatory weekly group sessions led by a dietitian, behaviour therapist or exer- cise therapist and, in the last 6 months (weeks 27 to 52), patients are offered monthly support sessions, which they can choose to access. All patients receive OPTIFAST ®900 as full meal replace- ments starting at week 2. Patients consume 4 MR shakes per day for a total of 900 kcal per day, a regimen that is high in proteins (90g/day) and moderate in carbohydrates (67 g/day). Patients with initial body mass indexes (BMIs) of 33 kg/m 2or higher commit to 12 weeks of full MRs, while patients with initial BMIs below 33 start with 6 weeks of full MRs and the option to increase to up to 12 weeks of full MRs. Once patients have completed their full MR regimen, there is a 5-week transition period to regular food, typi- cally followed by a maintenance diet, as determined in a one-on- one dietitian counselling session. Clinical care During the ﬁrst 6 months at the OHWMC, physician visits occur weekly, and medications are adjusted as needed. After 6 months, J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–6057 patients may attend monthly support groups, but follow up with the OHWMC physician is booked as needed with respect to weight management. Patients return to their primary care physicians at 6 months for ongoing regular medical monitoring, including man- agement of diabetes medications. For patients with type 2 diabetes who are on full MR, the clinic protocol is ﬁrst to reduce weight-gaining medications (Group WG). Within Group WG, priority is given to decreasing medications that have hypoglycemic effects and, subsequently, other weight-gaining medications. Finally, weight-neutral medications (Group WN) may be reduced if clinically indicated. Group WG includes patients taking insulin, sulfonureas (SUs), thiazolidinediones (TZDs) and/or meglitinides. Patients in Group WG may also be on weight-neutral medications. Group WN is composed of patients taking solely metformin and alpha-glucosidase inhibitors (AGIs). The data col- lected for this study predates the availability of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors in Canada. Dipeptidyl peptidase-4 (DPP-4) inhibi- tors had just been introduced in Canada, and the rare patients who were taking DPP-4 inhibitors were also taking weight-gaining hypo- glycemic agents and, therefore, were accounted for in Group WG. The percentage of reduction of hypoglycemic agents is at the dis- cretion of the treating physician but typically is a reduction of 30% to 50% of insulin the night prior to starting OPTIFAST ®900 shakes and a 50% reduction of medications that include risks for hypogly- cemia, such as sulfonylureas, on the day of starting OPTIFAST ®900 shakes. Patients who present with well-controlled glucose levels have more aggressive discontinuation of hypoglycemic agents in order to avoid hypoglycemia. When patients transition back to regular food, diabetes medi- cations may once again be adjusted; the typical protocol is to avoid weight-gaining agents in Group WG and preferentially selecting or increasing medications in Group WN. However, if patients are trying to avoid insulin use and are already on maximum levels of Group WN medications, another agent from Group WG may be prescribed. Statistical methods All data were prospectively collected in a registry. Consecutive patients with type 2 diabetes (deﬁned as fasting glucose levels of 7.0 mmol/L or higher or A1C levels of 6.5% or higher on 2 separate occasions) who had given consent to participate in the registry were included. Patients were excluded if there was noncompliance in the behavioural program, deﬁned as 1) taking less than 50% of the MRs or 2) attending fewer than 6 sessions in the program. Baseline and 6-month hypoglycemia medications, weights and glycemic pro- ﬁles were collected. The medications for patients in Group WG were compared with those for Group WN. Categorical variables were expressed as percentages and con- tinuous variables as mean±standard deviation. Continuous and cat- egorical variables were compared between Group WG and Group WN using ANOVA and the chi-square test, as appropriate. Weight and A1C levels were compared at baseline and at 6 months, with repeated measures by ANOVA using a mixed between-within subject analysis. Medications for diabetes at 6 months were categorized as discontinued, decreased in dosage, increased in dosage or added as new agents. Missing data were imputed by using multiple impu- tations with the previous observation carried forward. Linear regres- sion modelling was conducted to account for differences in baseline demographics, which could affect weight loss. All analyses were per- formed using SPSS 18.0 statistical software (IBM, Armonk, New York). Results Overall, glycemic data were available for 2744 patients; 456 (20.1%) were identiﬁed as having type 2 diabetes, and 91 (3.3%) ashaving impaired fasting glucose. In patients with type 2 diabetes, 95 (20.8%) were not taking medications for diabetes. Of the 361 patients (79.2%) who were taking medications for diabetes, 44 were excluded for noncompliance with the program. Of the 317 patients included in this study, 235 (74.1%) were in Group WG, and 82 (25.9%) were in Group WN. The baseline characteristics of the 317 patients with type 2 dia- betes and taking medications are described in Table 1 . In Group WG and Group WN, there were no signiﬁcant differences in age, gender, baseline weights or initial BMIs or in patients with initial BMIs below 33 or on the 6-week or 12-week MRs. However, baseline A1C levels were signiﬁcantly lower in Group WN than in Group WG (p<0.001). Baseline diabetes medications included 72.2% metformin, 43.8% SUs, 23.3% insulins, 20.8% TZDs, 2.8% AGIs, 1.3% meglitinides and 0.9% DPP-4 inhibitors. Decrease or discontinuation of medications over 6 months by medication classes were as follows: 92.1% SUs, 86.5% insulins, 78.8% TZDs, 77.8% AGIs, 50% meglitinides, 33.3% DPP-4s and 32.8% metformin ( Table 2 ). The only medication that was increased in dosage from baseline was metformin (3.5%), and rarely was a new medication added for glycemic control by 6 months: SUs, 6 patients; metformin, 17 patients; TZDs, 4 patients; DPP-4 inhibitors, 2 patients. Changes in weight and A1C levels from baseline to 6 months and in diabetes medications are shown in Table 3 . Differences in baseline A1C levels between Group WG and Group WN did not affect the percentages of weight. There was no signiﬁcant difference in per- centage of weight loss between Group WG and Group WN. At 6 months, in those who continued to take diabetes medications (223 patients) compared with patients who were no longer taking medi- cations for diabetes (94 patients), the percentage of weight loss was signiﬁcantly lower (16.0% vs. 18.6%; p=0.002). Baseline versus 6-month A1C levels by groups were: 7.5% vs. 6.7% (p<0.0001) for Group WG; 6.6% vs. 5.8% (p<0.0001) for Group WN; 7.4% vs. 6.0% (p<0.0001) for patients taking no medications at 6 months; and 7.2% vs. 6.6% (p<0.0001) for patients who were still taking medica- tions. A1C levels were signiﬁcantly lower in Group WN than in Group WG (p<0.0001). Discussion To our knowledge, the current study is the largest reported cohort concerning changes in hypoglycemic agents in patients with dia- betes following an intensive lifestyle program in conjunction with a full MR LCD diet. The key ﬁndings in our study include the following: 1. The protocol of reducing medications that are weight gaining ﬁrst and then weight-neutral medications appears to be safe, allowing for signiﬁcant improvement in A1C levels in the 6-month protocol. Table 1 Baseline characteristics of 317 patients with obesity and diabetes and taking medications Group WG (235) Group WN (82) p value Age (SD) 51.8 (9.2) 49.7 (9.9) NS Female (%) 121 (51.5%) 57 (69.5%) NS Initial weight in lbs (SD) 281.6 (58.3) 274.4 (51.5) NS Initial BMI kg/m 2(SD) 44.0 (8.6) 44.8 (7.6) NS Patients with BMI<33 (%) 8 (3.4%) 2 (2.4%) NS Patients on 6 weeks of MR (%) 26 (11.1%) 10 (12.2%) NS Patients on 12 weeks of MR (%) 209 (88.9%) 72 (87.8%) NS Baseline A1C 7.5% 6.6% p<0.001 A1C, glycated hemoglobin; BMI, body mass index; Group WG, Group weight-gain medications; Group WN, Group weight-neutral medications; MR, meal replace- ment; SD, standard deviation. J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–60 58 2. A number of diabetes medications were either discontinued or reduced, including SUs (92.1%), insulins (86.5%) and metformin (32.8%). 3. Patients who were able to discontinue all diabetes medica- tions at 6 months appeared to have greater reductions in per- centage of weight loss. 4. At 6 months, patients who were originally taking weight- neutral medications had better glycemic control than patients on weight-gaining diabetes medications. Previous data about weight loss and glycemic control have been limited to small cohorts. Harder et al showed that a full MR-LCD of 850 kcal/day resulted in an 11% weight loss in 11 patients with obesity and type 2 diabetes at 8 weeks. However, only 4 of the 11 patients were originally taking hypoglycemic agents, and they were discontinued before MR commencement (14) . In a retrospective review by Anderson et al of 183 obese individuals who were on a full MR-LCD (800 kcal/day) but with the possibilities of increasing to 1000 kcal/day, 50 patients had diabetes. Of these patients, 44 were taking hypoglycemic agents and, with weight loss, there was a 53.8% discontinuation of medications overall and a 68% reduction of medi- cations for those who lost more than a 100 pounds (15) . A study by Collins et al of 32 patients with type 2 diabetes reported an average 14.8% reduction of initial weight after following a 12-week 800 kcal per day diet (half the patients were on full MRs, the other half were on partial MRs with food to achieve a minimum of 800 kcal per day). At 1 year, subjects maintained an average of 58.8% of the weight loss over the diet period. A1C values at baseline, week 12 (end of LCD) and 1-year follow up were, respectively, 8.4%, 6.6% and 8.1%, with no statistical differences between baseline and year 1. At week 12, 6 of the 8 participants taking insulin discontinued that medication, while the other 2 had a 71% reduction in dosage. At 1-year follow up, 1 participant had restarted insulin. By the end of the LCD, 17 of the participants (71%) had discontinued oral hypoglycemics, and the remaining 7 subjects reduced medication needs by 75%. At the 1-year follow up, 13 of the 24 patients (54%) remained off oral hypoglycemic medications (13) . A small study by Plum et al compared 14 patients with obesity and type 2 diabetes before and after an equivalent amount of weight loss induced by either LCD (patients on full MR of 800 kcal per day) or Roux-en-Ygastric bypass (RYGB). Patients taking TZDs and insulin were excluded. There was a mean reduction of 8.1% in total body weight (7 patients on LCD at week 8; 7 patients after RYGB at week 3.4). A1C levels were reported only at initial weight: A1C 7.8% (LCD) and 7.5% (RYGB). The disposition index (insulin secretion normalized to the degree of insulin resistance) improved in both groups, but the absolute increase was greater after RYGB. Antidiabetes medica- tions were discontinued after RYGB contrasting with a 55% reduc- tion in the number of medications after LCD (16) . Like the above ﬁndings, our study provides detailed accounts of changes in medi- cations and separates differing cohorts based on the diabetes regi- mens and their resultant responses, including percentages of weight changes and A1C levels. As hypothesized, weight and diabetes medi- cations decreased during the program, but an interesting ﬁnding was that the patients who had discontinued all diabetes medica- tions at 6 months had signiﬁcantly better weight loss, and those who were originally taking weight-neutral medications had the best resultant A1C levels at the end of the program. Our study is also the largest assessment of patients with type 2 diabetes taking full MR-LCD in a real-world setting. Although the Look AHEAD (Action for Health in Diabetes) study included a larger patient population, a partial MR protocol was utilized in the inten- sive lifestyle intervention arm (ILI). At 1 year, the ILI arm showed an 8.5% weight loss; 25% of ILI participants were no longer prescribed diabetes medications (compared with 12% in diabetes and support education); and insulin use decreased from 15% at baseline to 13% (17) . In contrast, at 6 months, we observed an approximately 16% weight loss; 30% of patients were no longer prescribed diabetes medications; and we found insulin discontinuation or decrease of 86.5%. Although our study describes results at 6 months, evidence from randomized intervention trials supports the ﬁnding that the greater initial weight loss produced by MR diets improves long- term weight maintenance, provided it is followed by a 1- to 2-year integrated weight-maintenance program consisting of lifestyle inter- ventions that involve dietary change, nutrition education, behaviour therapy and increased physical activity (18) . Intentional weight loss of 7% to 14% may be required for full discontinuation of at least 1 hypoglycemic medication, whereas discontinuation of insulin may be achieved at a mean weight reduction of 11% of initial body weight (19) . Therefore, compared with a partial MR diet in which there can Table 2 Changes in diabetes medications Medication Baseline N (% of 317 patients)Changes in medications at 6 months compared with baseline Discontinued n (% discontinued)Decreased dosage n (% decreased)Increased dosage n (% increased) Sulfonurea 139 (43.8%) 120 (86.3%) 8 (5.8%) - Thiazolidinediones 66 (20.8%) 48 (72.7%) 4 (6.1%) - Insulin 74 (23.3%) 33 (44.6%) 31 (41.9%) - Meglitinides 4 (1.3%) 2 (50%) - - Metformin 229 (72.2%) 51 (22.3%) 24 (10.5%) 8 (3.5%) Alpha-glucosidase inhibitor 9 (2.8%) 7 (77.8%) - - DPP-4 inhibitor 3 (0.9%) 1 (33.3%) - - DPP-4, dipeptidyl peptidase-4. Table 3 Weight and A1C levels based on medications Wt lbs baseline (SD) Wt lbs 6 mo (SD) % wt loss (SD) A1C baseline (SD) A1C 6 mo (SD) p Group WG 281.7 (58) 233.8 (48) 16.7% (6.7) 7.5% (1.4) 6.7% (1.6) p<0.0001 Group WN 274.0 (51) 227.4 (44) 16.8% (6.9) 6.6% (1.2) 5.8% (1.3) * p<0.0001 No meds at 6 months (94 patients) 281.2 (61) 227.7 ((48) 18.6% (6.5) † 7.4% (1.2) 6.0% (0.8) p<0.0001 Taking medications at 6 months (223 patients) 279.1 (55) 234 (47) 16.0% (6.7) 7.2% (1.4) 6.6% (1.6) p<0.0001 A1C, glycated hemoglobin; Group WG, Group weight-gain medications; Group WN, Group weight-neutral medications; mo, month; Wt, weight. * A1C levels were signiﬁcantly different in Group WG and Group WN (p<0.0001). †Percentage of weight loss was signiﬁcantly greater in patients taking no medications at 6 months compared with patients still taking medications (p=0.002). J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–6059 be more variability in energy intake, in our cohort, the effect of a full MR diet on weight loss and changes in medications could be expected to be superior. This is the ﬁrst study to categorize diabetes medications based on their weight-gaining or weight-neutral properties. This study of 317 patients with type 2 diabetes demonstrates that the protocol of reducing medications that are weight-gaining ﬁrst and then reduc- ing weight-neutral medications appears to be safe and involves no signiﬁcant compromise of A1C levels in the 6-month protocol. There were no signiﬁcant differences in weight loss between Group WG and Group WN. When comparing the 6-month changes in medi- cations, the decrease in or discontinuation of hypoglycemic agents is extensive, ranging from 50% to 92.1% for Group WG and 32.8% to 72.8% for Group WN. The signiﬁcant changes in weight at 6 months were observed, even accounting for differences between baseline A1C levels between groups. The protocol for patients with diabetes on full MR-LCD is to decrease weight-gaining and hypo- glycemic agents ﬁrst and then, only if necessary, weight-neutral hypoglycemic agents. Reintroduction of medications for glycemic control may be necessary when patients increase intake of regular food, but it has been minimal. In fact, what is impressive is that by 6 months, of patients who were taking insulin at baseline, 44.6% discontinued the medication, and 41.9% decreased the dosage. It is reassuring that despite reduction of hypoglycemic agents, glyce- mia levels improved, such that at 6 months, patients were at lower weights and had improved glycemic control, thus requiring less medication. Patients who particularly beneﬁted from the full MR-LCD were patients who were able to have all their diabetes medica- tions discontinued by 6 months (this group experienced the great- est amount of weight loss: 18.6%) and those who had initially been on weight-neutral diabetes medications (had the best A1C pro- ﬁles at the end of the program; A1C levels at 6 months were 5.8% compared with baseline levels of 6.6 %). Therefore, at the very least, glucose levels are safely maintained for patients with diabetes involved in a full MR-LCD 6-month lifestyle program and require fewer medications. This practice appears to be safe and to involve no signiﬁcant compromise of A1C levels, irrespective of the cat- egory of diabetes medications. This should reassure clinicians about the use of various classes of medications in patients entering a full MR weight-loss program. Certainly, there are some limitations in our study. First, this is a retrospective cohort, and the rationales for choices of initial dia- betes medications cannot be elucidated. Second, our analysis was restricted to weight and glycemic control in patients with obesity and diabetes taking medications at 6 months. As patients transitioned back to the community for their diabetes manage- ment, we were unable to obtain 1-year data consistently. Although our study lacks length of follow up compared to other behavioural obesity-study interventions, it has the distinction of being the largest reported cohort of patients with diabetes taking medications who have been drawn from a signiﬁcant database of several thousand patients on a standardized full MR-LCD behavioural program. A ﬁnal limitation is that our data cannot be extrapolated to novel glyce- mic agents introduced in Canada. In 2009, there was the introduc- tion of a new class of weight-neutral medication for diabetes, DPP-4 inhibitors. In 2010 and 2015, there was the approval of a poten- tial weight-losing medication class, GLP-1 agonists, and subse- quently, in 2014, SGLT2 inhibitors. Data collected from the CORE program was limited to years before 2009 so as to mitigate the evolv- ing landscape of new hypoglycemic agents approved by Health Canada since 2010. Future analysis in the context of these novel agents will be required.Conclusions Patients who are trying to control their weight often face bar- riers that make weight management more diﬃcult. Barriers can be related to medications, mechanical problems (e.g. hernia, knee pain, sleep apnea), mood or situational effects (e.g. skipped meals, shift work). Full MR-LCD behaviour programs can be regulated for strategic breaking of the cycle that patients are caught in with respect to their weight, allowing patients to achieve lower weights and sub- sequently “reset” themselves. One signiﬁcant barrier to treatment of obesity can be weight-gaining medications for diabetes management. This study demonstrates that we can safely reduce weight-gaining medications in patients with diabetes by using a full MR-LCD behaviour program, and this can achieve signiﬁcant weight loss without compromising glycemic control. References 1.Wing RR. Weight loss in the management of type 2 diabetes. In: Gerstein BH, ed. Evidence-based diabetes care. Toronto: B.C. Decker, 2001, pg. 252–76. 2.Conway B, Miller RG, Costacou T, et al. Temporal patterns in overweight and obesity in type 1 diabetes. Diabet Med 2010;274:398–404. 3.UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes: UKPDS 33. Lancet 1998;3529131:837–53. 4.Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes 1998;475:699–713. 5.Johnston BC, Kanters S, Bandayrel K, et al. Comparison of weight loss among named diet programs in overweight and obese adults: A meta-analysis. JAMA 2014;3129:923–33. 6.Dent R, Harper ME, McPherson R, et al. Effect of treatment regimen on weight loss in response to energy restrictionin patients with type 2 diabetes: Lessons from the Ottawa Hospital Weight Management Clinic database of 3314 patients. Obesity 2013; The 31st Annual Scientiﬁc Meeting of the Obesity Society: S226. 7.Jensen MD, Ryan DH, Donato KA, et al. Guidelines 2013 for managing over- weight and obesity in adults. Obesity (Silver Spring) 2014;22(Suppl. 2):S93. 8.Redmon JB, Raatz SK, Reck KP, et al. One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: A randomized trial. Diabetes Care 2003;269:2505–11. 9.Li Z, Hong K, Saltsman P, et al. Long-term eﬃcacy of soy-based meal replace- ments vs an individualized diet plan in obese type II DM patients: Relative effects on weight loss, metabolic parameters, and C-reactive protein. Eur J Clin Nutr 2005;593:411–18. 10. Look AHEAD Research Group. Eight-year weight losses with an intensive life- style intervention: The look AHEAD study. Obesity (Silver Spring) 2014;221:5– 13. 11. Asnani S, Richard BC, Desouza C, Fonseca V. Is weight loss possible in patients treated with thiazolidinediones? Experience with a low-calorie diet. Curr Med Res Opin 2003;197:609–13. 12. Capstick F, Brooks BA, Burns CM, et al. Very low calorie diet VLCD: A useful alter- native in the treatment of the obese NIDDM patient. Diabetes Res Clin Pract 1997;362:105–11. 13. Collins RW, Anderson JW. Medication cost savings associated with weight loss for obese non-insulin-dependent diabetic men and women. Prev Med 1995;244:369–74. 14. Harder H, Dinesen B, Astrup A. The effect of a rapid weight loss on lipid proﬁle and glycemic control in obese type 2 diabetic patients. Int J Obes Relat Metab Disord 2004;281:180–2. 15. Anderson JW, Jhaveri MA. Reductions in medications with substantial weight loss with behavioral intervention. Curr Clin Pharmacol 2010;54:232–8. 16. Plum L, Ahmed L, Febres G, et al. Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss. Obesity (Silver Spring) 2011;1911:2149–57. 17. Redmon JB, Bertoni AG, Connelly S, et al. Effect of the Look AHEAD study inter- vention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes. Diabetes Care 2010;336:1153–8. 18. Astrup A, Rossner S. Lessons from obesity management programmes: Greater initial weight loss improves long-term maintenance. Obes Rev 2000;11:17– 19. 19. Kumar AA, Palamaner Subash SG, Kahan S, et al. Intentional weight loss and dose reductions of anti-diabetic medications: A retrospective cohort study. PLoS ONE 2012;72:e32395. J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–60 60 There are 4 articles provided only 2 are needed and it only has to be one paragraph. And it also has to go throught turn it in. So please no plagerism. On the discussion board, using a minimum of two Applied nutritional investigation Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes Talib A. Hussain M.B., Ch.B., R.C.G.P. a, Thazhumpal C. Mathew M.Sc., Ph.D., F.R.C.Path. b, Ali A. Dashti M.Sc., Ph.D. b, Sami Asfar M.B., Ch.B., M.D., F.R.C.S., F.A.C.S. c, Naji Al-Zaid B.Sc., Ph.D. d, Hussein M. Dashti M.D., Ph.D., F.I.C.S., F.A.C.S. c,* aAl Shaab Family Medicine Medical Center, Ministry of Health, KuwaitbDepartment of MLS, Faculty of Allied Health Sciences, Health Sciences Center, Kuwait University, KuwaitcDepartment of Surgery, Faculty of Medicine, Health Sciences Center, Kuwait University, KuwaitdDepartment of Physiology, Faculty of Medicine, Health Sciences Center, Kuwait University, Kuwait article info Article history: Received 13 June 2011 Accepted 16 January 2012 Keywords: Obesity Body mass index Blood glucose Lipid pro ﬁle Ketogenic diet Low-calorie diet abstract Objective: Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneﬁ cial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the bene ﬁcial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. Methods: Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. Results: The LCD and LCKD had bene ﬁcial effects on all the parameters examined. Interestingly, these changes were more signiﬁ cant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically signi ﬁcant. Conclusion: This study shows the bene ﬁcial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can signi ﬁcantly lower blood glucose levels. 2012 Elsevier Inc. All rights reserved. Introduction The current increase in the rate of type 2 diabetes is quite alarming. During the past three decades, the prevalence of this disease in the middle-aged has almost doubled . According to reports by the World Health Organization, approximately 170 million people worldwide have diabetes and this ﬁgure is expected to reach to 366 million by 2030 . A similar trend in the increase of type 2 diabetes has been observed in the Gulf region, especially in Kuwait [3,4]. The risk of diabetes is strongly associated with obesity, and even a modest weight loss has been reported to substantially decrease the diabetic risk. According to statistics from the US Center for Disease Control and Prevention, 55% of diabetic patients are obese and 85% are overweight . In several previous * Corresponding author. Tel.: þ965-2498-6226; fax: þ965-2531-9597. E-mail address: [email protected] (H. M. Dashti). 0899-9007/$ - see front matter 2012 Elsevier Inc. All rights reserved. doi: 10.1016/j.nut.2012.01.016 Contents lists available at ScienceDirect Nutrition journal homepage:www.nutritionjrnl.com Nutrition 28 (2012) 1016 –10 21 studies, we have shown that a low-carbohydrate ketogenic diet (LCKD) is quite effective in decreasing body weight[6–13 ] . The LCKD has a low-carbohydrate content (20– 30 g/d) that causes ketosis and mimics the physiologic state of fasting . Before the advent of exogenous insulin, dietary modi ﬁcation was the main therapy for diabetes. However, the diet recom- mendations during that time were completely different from the current low-fat, high-carbohydrate dietary recommendations for patients with diabetes [14,15]. For example, Dr. Elliot Joslin ’s Diabetic Diet in 1923 consisted of meats, poultry, ﬁsh, clear soups, gelatin, eggs, butter, olive oil, coffee, and tea, providing approx- imately 5% of energy from carbohydrates, 20% from protein, and 75% from fat . During that time, a diabetic diet with a similar composition was advocated by Dr. Frederick Allen . In a previous study from our laboratory, we quite convinc- ingly showed the beneﬁ cial effects of a ketogenic diet in obese diabetic subjects . Furthermore, in recent studies in an animal model of diabetes, we showed that the LCKD has a signi ﬁcant beneﬁ cial effect on ameliorating the diabetic state and helping to stabilize hyperglycemia [11,13]. From the results of these studies, we recommended that the LCKD may be effective in diabetes management by improving glycemia and decreasing the need for medication. The present study, therefore, is a continuation of our previous studies in diabetic patients and experimental diabetic animals. The main purpose of the therapeutic plan of this study was to evaluate the effects of administering a low-calorie diet (LCD) and an LCKD for 24 wk in improving glycemia and decreasing the need for diabetic medication in overweight and obese patients with type 2 diabetes. Materials and methods Participants In this study, the participants were recruited from the Al-Shaab Family Medicine Medical Center, Kuwait. The participants were included in this study if they were at least 18 y old, had a body mass index higher than 25 kg/m 2and a fasting serum glucose level higher than 125 mg/dL ( >6.9 mmol/L). Patients with evidence of renal insuf ﬁciency, liver disease, or unstable cardiovascular disease by history, physical examination, and laboratory tests were excluded from the study. All participants provided written informed consent, and the study was approved by Kuwait University. Intervention The participants were given detailed information on the LCKD and LCD during their initial visit. They were then advised to take choose an LCD or an LCKD, depending on their preference. Initially, participants in the LCKD group were instructed to follow the LCKD as individuals or in small groups, with an initial goal of w20 g/d of carbohydrate. The list of recommended and restricted foods in the LCKD is presented in Table 1. The participants were given previous reports on the LCKD from our labora- tory, a handout, and a handbook [6–13 ] concerning the type and amount of foods Table 1 Recommended and restricted food in a low-carbohydrate ketogenic diet and a sample low-calorie diet Recommended food in low-carbohydrate ketogenic diet Proteins ﬁsh: tuna, sardine prawns, shrimps, lobster meat; kebabs; sausages; minced poultry; chicken; eggs; cheese: full-fat cheese Vegetables/fruits spinach, watercress, eggplant, parsley, mulberry, coriander, mint, artichoke, okra, cabbage, mushroom, avocado, leek, carrot, radish, celery, cauli ﬂower, green pepper, lettuce, cucumber, tomato, 10 –15 olives/d, lemon, strawberry 6/d, avocado, berries 10/d Oil olive oil (5 tbsp, added to salad),ﬂax seed oil Restricted food in low-carbohydrate ketogenic diet ﬂour, potato, macaroni spaghetti, noodles, bread, rice, sugar, sweets, honey, cakes, all fruit juices, all soft drinks Sample 2200-calorie low-calorie diet Breakfast coffee with caffeine (12 oz); cottage cheese 1% fat (1.5 cup); cream, ﬂuid, half and half (1 tbsp); fruit cocktail (0.5 cup) Morning snack medium apple with peel, medium banana (1 each) Lunch medium apple with peel (1 each); bread whole wheat slice (2 each); cheddar cheese (2 in. 3); mayonnaise (tuna salad, 0.15 cup); turkey breast/white meat (3 oz) Afternoon snack Bread slice rye 7 grain (2 each); jelly: any fruit ﬂavor (4 tsp); peanut butter (2 tbsp) Dinner chicken breast/white meat (4 oz); rice: white cook steamed (1.5 cups); low-calorie thousand island dressing (salad); Kraft mayonnaise (4 tbsp); croutons (cook cuts bred into small cubes) plain (0.25 cup); 1 small garden salad with tomato, onion Table 2 Baseline values of different physical and biochemical parameters monitored in diabetic and non-diabetic subjects consuming an LCD or an LCKD Total Diabetic Non-diabeticLCD LCKD LCD LCKD Age 37.2 0.4 45.1 1.1 39.2 0.7 34.8 0.7 36.8 0.6 Weight 96.0 0.9 95.7 2.0 104.0 2.1 91.0 1.6 95.7 1.3 Fasting blood sugar 6.3 0.1 9.0 0.6 9.1 0.3 5.3 0.1 5.4 0.1 Triacylglycerols 1.8 0.1 2.5 0.2 2.2 0.1 1.5 0.1 1.7 0.1 Total cholesterol 5.3 0.1 5.5 0.2 5.7 0.1 5.0 0.1 5.2 0.1 LDL 3.0 0.1 3.4 0.2 3.4 0.1 2.7 0.1 2.8 0.1 HDL 1.0 0.0 1.0 0.1 1 0.1 1.1 0.0 1.0 0.0 Uric acid 303.2 4.0 328.5 12.0 307.8 9.0 284.8 7.0 311.8 6.4 Creatinine 75.0 0.8 76.7 2.9 74.2 1.6 76.1 1.6 74.2 1.1 Urea 4.5 0.1 4.7 0.2 5.0 0.2 4.4 0.1 4.4 0.1 Waist circumference 110.2 0.6 113 1.7 115.3 1.2 107.7 1.1 108 0.9 HbA1c 7.9 0.1 8.2 0.3 7.8 0.1 Body mass index 37.3 0.3 36.3 0.5 40.0 0.7 36.0 0.6 37.2 0.5 HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; LCD, low-calorie diet; LCKD, low-carbohydrate ketogenic diet; LDL, low-density lipoprotein Data are expressed as mean SE T. A. Hussain et al. / Nutrition 28 (2012) 1016 –10 21 1017 they could eat and the types of food that should be avoided. Initially, the participants were allowed to eat unlimited amounts of meats, poultry,ﬁsh, and eggs. In addition, the participants were asked to take 2 cups of salad vegetables per day, hard cheese (100 –120 g), and limited amounts of cream, olives, and lemon juice. Although fats and oils were allowed, the participants were instructed not to take trans-fats. Antidiabetic medications were decreased with the diet initiation. In general, the insulin doses were halved and the sulfonylurea doses were halved or discontinued. The participants also were instructed to take a standard multivitamin/multimineral tablet and drink approximately six to eight glasses of water daily. The participants returned every other week for 24 wk for further counseling on diet and medication. When a participant neared half the weight loss goal or developed cravings, he or she was advised to increase the carbohydrate intake by approximately 5 g/d each week as long as the weight loss continued. The participants could choose 5-g carbohydrate portions from one of the following foods each week: salad vegetables, low-carbohydrate vegetables, hard or soft cheese, nuts, or low-carbohydrate snacks. The participants in the LCD group were given appropriate guidelines and a sample LCD menu of 2200 calories is pre- sented in Table 1. The initial dose of some antidiabetic medications was decreased to half in the LCKD group at the beginning of the dietary program. The antidiabetic medication dosage was modi ﬁed based on twice-daily glucometer measurements and hypoglycemic episodes, and diuretic and other antihypertensive medication adjustments were based on the orthostatic symptoms, blood pressure, and lower extremity edema. Measurements The participants were given written instructions on how to complete the food records. All participants completed the take-home food record according to the directions. These food records were collected at the beginning of the study and at weeks 2, 8, 12, 16, 20, and 24. The anthropometric and vital sign measurements and assessments for hypoglycemic episodes and other symptomatic side effects were performed every other week. Weight was measured on a standardized digital scale while the participant was wearing light clothes and without shoes. Blood pressure was measured after the participant had been seated quietly without talking for 3 min. Hypoglycemic episodes and symptomatic side effects were assessed by direct questioning of the participant. Blood specimens were collected after the participant had fasted overnight at weeks 0, 4, 8, 12, 16, 20, and 24. The following serum tests were performed in the hospital laboratory using standardized methods: complete blood cell count and lipid, liver, and renal pro ﬁles. For statistical analysis of the data, a paired ttest was used to determine the statistical signi ﬁcance between weeks 1 and 24 in the different groups and an independent ttest was used to analyze the signiﬁ cance between the LCD and LCKD groups using SPSS 16 (SPSS, Inc., Chicago, IL, USA). The method used in this study for estimating the treatment effects was with completers only, rather than an intent-to-treat analysis. Results Three hundred sixty-three participants were enrolled in the study and completed the 24 wk of follow-up. Adherence to the two dietary programs was discussed with the participants and recorded. Adequate food records were available to determine each participant ’s adherence to the dietary program (data not shown). Among the 363 participants, 86 were men (23.7%) and 277 were women (76.3%). Among the men, 28 were diabetic and 58 were non-diabetic; among the women, 74 were diabetic and 203 were non-diabetic. In total, 102 participants were diabetic and 261 were non-diabetic. Concerning diet, 143 (27 men and 116 women) of the 363 participants were on a low-calorie diet, whereas 220 (59 men and 161 women) were on a ketogenic diet. In the LCD group, 24 participants (16.8%) were diabetic, whereas in the LCKD group 78 (35.5%) were diabetic. The baseline values of the clinical parameters examined are listed in Table 2. Effect on body weight, body mass index, and waist circumference There was a signi ﬁcant difference ( P< 0.0001) in the body weight, body mass index, and waist circumference of the diabetic and non-diabetic participants in the LCD and LCKD groups compared with their initial (week 1) and ﬁnal (week 24) measurements ( Fig. 1A,Table 3 ). The effectiveness of the LCKD over the LCD is quite evident in Figure 1A, which shows the percentage of weight loss in the different groups. Fig. 1. Changes in the percentage of body weight (A), blood glucose level (B), and level of glycosylated hemoglobin (C) in diabetic and non-diabetic subjects after the administration of a low-calorie diet or a low-carbohydrate ketogenic diet for 24 wk. A signi ﬁcant difference (P <0.0001) in body weight was noticed in the low-calorie and low-carbohydrate ketogenic diet groups compared with their initial (week 1) and ﬁnal (week 24) measurements. The ketogenic diet was more effective than the low-calorie diet. The blood sugar level signi ﬁcantly decreased in the two groups. The effectiveness of the low-carbohydrate ketogenic diet was much greater (P < 0.0001) in the diabetic group on the low-carbohydrate ketogenic diet than on the low-calorie compared with week 1 and week 24 blood glucose levels. In the dia- betic group, the glycosylated hemoglobin level signi ﬁcantly decreased with the low-carbohydrate ketogenic diet compared with the two diets. Black circles, ketogenic and non-diabetic; black triangles, ketogenic and diabetic; white circles, low calorie andnon-diabetic; white triangles, low calorie and diabetic. T. A. Hussain et al. / Nutrition 28 (2012) 1016 –1021 1018 Effect on blood glucose and glycosylated hemoglobin levelsAlthough the initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group, the blood sugar level signi ﬁcantly decreased in the two groups (Fig. 1 B,C). However, the effectiveness of the LCKD was much greater ( P < 0.0001) in the diabetic LCKD group than in the LCD group compared with the initial (week 1) and ﬁnal (week 24) blood glucose levels. Similarly, the glycosylated hemoglobin (HbA1c) level signi ﬁcantly decreased with the LCKD compared with the two diets in the diabetic group (Fig. 1 C). Effect on lipid pro ﬁle The effects of the LCD and LCKD on the lipid pro ﬁle of diabetic and non-diabetic participants are shown in Figure 2. Diabetic and non-diabetic participants in the LCKD group showed a signi ﬁcant decrease ( P< 0.0001) in triglycerides, total cholesterol, and low-density lipoprotein levels, whereas the Table 3 Effect of an LCD and an LCKD on body weight, body mass index, and waist circumference in diabetic and non-diabetic subjects Group Initial, mean SD Week 24, mean SD Change (%) P * Body weight (kg) Diabetic and LCD 95.71 9.56 89.02 5.97 7.0 <0.0001 Diabetic and LCKD 104.01 18.89 91.56 17.45 12.0 <0.0001 P y 0.005 0.275 <0.001 Non-diabetic and LCD 91.01 17.77 86.38 17.08 5.1 <0.0001 Non-diabetic and LCKD 95.71 15.58 83.87 14.82 12.4 <0.0001 P y 0.024 0.026 <0.001 Body mass index (kg/m 2) Diabetic and LCD 36.31 2.63 33.87 2.75 6.7 <0.0001 Diabetic and LCKD 39.84 6.40 35.05 5.90 12.0 <0.0001 P y 0.001 0.180 <0.001 Non-diabetic and LCD 35.97 6.06 34.14 5.86 5.1 <0.0001 Non-diabetic and LCKD 37.19 5.73 32.59 5.40 12.4 <0.0001 P y 0.097 0.026 Waist circumference (cm) Diabetic and LCD 113.92 8.43 109.94 9.07 3.5 <0.0001 Diabetic and LCKD 115.27 10.45 106.81 9.83 7.3 <0.0001 P y 0.563 0.168 <0.001 Non-diabetic and LCD 107.72 11.58 104.72 11.00 2.8 <0.0001 Non-diabetic and LCKD 108.74 10.50 102.10 9.36 6.1 <0.0001 P y 0.455 0.041 <0.001 LCD, low-calorie diet; LCKD, low-carbohydrate ketogenic diet *Signi ﬁcance between weeks 1 and 24 by paired ttest.ySigni ﬁcance between LCD and LCKD groups by independent ttest. Fig. 2. Changes in the lipid pro ﬁle in diabetic and non-diabetic subjects after the administration of a low-calorie diet or a ketogenic diet for 24 wk. Diabetic and non-diabetic participants in the low-calorie ketogenic diet group showed a signi ﬁcant decrease (P <0.0001) in triglycerides (A), total cholesterol (B), and LDL (D) levels, whereas the HDL level (C) was signi ﬁcantly (P <0.0001) increased. Black circles, ketogenic and non-diabetic; black triangles, ketogenic and diabetic; HDL, high-density lipoprotein; LDL, low- density lipoprotein; white circles, low calorie and non-diabetic; white triangles, low calorie and diabetic. T. A. Hussain et al. / Nutrition 28 (2012) 1016 –10 21 1019 high-density lipoprotein level was signiﬁcantly ( P< 0.0001) increased ( Fig. 2). Changes in urea, uric acid, and creatinine levels Urea levels were signi ﬁcantly increased for the two diet groups in diabetic and non-diabetic participants ( Fig. 3A). Interestingly, the uric acid level increased in the LCD group, whereas it decreased in the LCKD group ( Fig. 3B). A similar change was noted for the creatinine level (Fig. 3 C). Discussion The effect of carbohydrate restriction on type 2 diabetes was previously examined in our laboratory . We found that the body weight, body mass index, and levels of blood glucose, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and urea were signi ﬁcantly decreased from week 1 to week 56 ( P < 0.0001). Conversely, the level of high-density lipoprotein cholesterol was increased signi ﬁcantly ( P< 0.0001). These changes were more signi ﬁcant in subjects with a high blood glucose level as compared with those with a normal blood glucose level. Furthermore, we found that the cardiac protective and ultrastructural changes in the cardiac muscles of laboratory rats that were fed normal, high-carbohydrate, and low- carbohydrate ketogenic diets . We convincingly showed the therapeutic and protective effects of the LCKD in a diabetic rat model [11,13]. The present results showed that, in addition to its therapeutic value, an LCKD is safe to use for a longer period in obese diabetic subjects. Other investigators reported that HbA1c improved to a greater degree with an LCKD over 1 y compared with a low-fat, calorie-restricted diet [18,19]. Our results are in agreement with the previous similar studies carried out by other investigators [20– 22]. Furthermore, very LCKDs have not been found to have an adverse effect on glucose metabolism or insulin resistance [23– 25]. Also, the prolonged administration of very LCKDs has been reported to not cause any chronic dehydration . In the present 6-months ’dietary intervention, the LCKD resulted in a signi ﬁcant improvement of glycemia, as measured by the fasting glucose and HbA1c levels in patients with type 2 diabetes. More importantly, this improvement was observed after some antidiabetic medications had been decreased to half in the LCKD group. The present data showed that the participants in the two dietary programs exhibited decreases in body weight. Several recent studies have indicated that an LCKD is effective in improving glycemia. A few studies have shown that, in non- diabetic individuals, LCKDs are more effective than higher- carbohydrate diets at improving fasting serum glucose [27–31] and insulin [19,31–33] and at improving insulin sensitivity as measured by the homeostasis model [5,6] . F urthermor e, other investigators have reported that antidia- betic medications were decreased in some participants of the dietary program [19,21,22]. Based on the theoretical effects of the LCKD , the observed effects of the diet on body water by bioelectric impedance and practical experience with the diet  , the continuation of antidiabetic medication in patients who are on an LCKD should be cautiously monitored. Until we learn more about using LCKDs, the medical monitoring for hypogly- cemia, dehydration, and electrolyte abnormalities is imperative in patients taking antidiabetic or diuretic medications. Although body weight decreased signi ﬁcantly in these 102 diabetic participants, the mean weight loss was less compared with what we observed in participants consuming an LCKD in a similar previous trial ( 12.0 kg) . Because the diabetic participants had a higher baseline mean weight than the participants consuming an LCKD in our previous trial, this translates into an even more dramatic disparity in the percentage of change in body weight. It should be noted that in the present study, most participants were taking insulin and/or oral hypoglycemic agents that are known to induce weight gain Fig. 3. Changes in the levels of urea (A), uric acid (B), and creatinine (C) after the administration of a low-calorie diet or a ketogenic diet for 24 wk in diabetic and non-diabetic subjects. Urea levels were signi ﬁcantly increased in the two diet groups in diabetic and non-diabetic participants. Uric acid level increased in the low-calorie diet group but decreased in the low-carbohydrate ketogenic diet groups. A similar change was noticed for the creatinine level. Black circles, keto- genic and non-diabetic; black triangles, ketogenic and diabetic; white circles, low calorie and non-diabetic; white triangles, low calorie and diabetic. T. A. Hussain et al. / Nutrition 28 (2012) 1016 –1021 1020 [36–38]. Moreover, these same agents, particularly insulin, inhibit ketosis, which is strived for in the earliest phases of the LCKD. Although it remains unclear whether ketones actually play a role in weight loss on the LCKD, previous research in non-diabetic patients has shown a positive correlation between the level of ketonuria and a success in weight loss . The main limitations of our study are its small sample and short duration. Conclusion In summary, the LCKD had signi ﬁcant positive effects on body weight, waist measurement, serum triacylglycerols, and glyce- mic control in participants with type 2 diabetes. Most impres- sively, there was an improvement in HbA1c despite the small sample and short duration of follow-up, and this improvement in glycemic control occurred after the antidiabetic medications had been decreased substantially in participants using the LCKD program. 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