Osama Hamdy

Prevention and management of type 2 diabetes: dietary components and nutritional strategies

In the past couple of decades, evidence from prospective observational studies and clinical trials has converged to support the importance of individual nutrients, foods, and dietary patterns in the prevention and management of type 2 diabetes. The quality of dietary fats and carbohydrates consumed is more crucial than is the quantity of these macronutrients. Diets rich in wholegrains, fruits, vegetables, legumes, and nuts; moderate in alcohol consumption; and lower in refined grains, red or processed meats, and sugar-sweetened beverages have been shown to reduce the risk of diabetes and improve glycaemic control and blood lipids in patients with diabetes. With an emphasis on overall diet quality, several dietary patterns such as Mediterranean, low glycaemic index, moderately low carbohydrate, and vegetarian diets can be tailored to personal and cultural food preferences and appropriate calorie needs for weight control and diabetes prevention and management. Although much progress has been made in development and implementation of evidence-based nutrition recommendations in developed countries, concerted worldwide efforts and policies are warranted to alleviate regional disparities.

Roux-en-Y Gastric Bypass Surgery or Lifestyle With Intensive Medical Management in Patients With Type 2 Diabetes: Feasibility and 1-Year Results of a Randomized Clinical Trial

IMPORTANCE Emerging data support bariatric surgery as a therapeutic strategy for management of type 2 diabetes mellitus. OBJECTIVE To test the feasibility of methods to conduct a larger multisite trial to determine the long-term effect of Roux-en-Y gastric bypass (RYGB) surgery compared with an intensive diabetes medical and weight management (Weight Achievement and Intensive Treatment [Why WAIT]) program for type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS A 1-year pragmatic randomized clinical trial was conducted in an academic medical institution. Participants included persons aged 21 to 65 years with type 2 diabetes diagnosed more than 1 year before the study; their body mass index was 30 to 42 (calculated as weight in kilograms divided by height in meters squared) and hemoglobin A1c (HbA1c) was greater than or equal to 6.5%. All participants were receiving antihyperglycemic medications. INTERVENTIONS RYGB (n = 19) or Why WAIT (n = 19) including 12 weekly multidisciplinary group lifestyle, medical, and educational sessions with monthly follow-up thereafter. MAIN OUTCOMES AND MEASURES Proportion of patients with fasting plasma glucose levels less than 126 mg/dL and HbA1c less than 6.5%, measures of cardiometabolic health, and patient-reported outcomes. RESULTS At 1 year, the proportion of patients achieving HbA1c below 6.5% and fasting glucose below 126 mg/dL was higher following RYGB than Why WAIT (58% vs 16%, respectively; P = .03). Other outcomes, including HbA1c, weight, waist circumference, fat mass, lean mass, blood pressure, and triglyceride levels, decreased and high-density lipoprotein cholesterol increased more after RYGB compared with Why WAIT. Improvement in cardiovascular risk scores was greater in the surgical group. At baseline the participants exhibited moderately low self-reported quality-of-life scores reflected by Short Form-36 total, physical health, and mental health, as well as high Impact of Weight on Quality of Life-Lite and Problem Areas in Diabetes health status scores. At 1 year, improvements in Short Form-36 physical and mental health scores and Problem Areas in Diabetes scores did not differ significantly between groups. The Impact of Weight on Quality of Life-Lite score improved more with RYGB and correlated with greater weight loss compared with Why WAIT. CONCLUSIONS AND RELEVANCE In obese patients with type 2 diabetes, RYGB produces greater weight loss and sustained improvements in HbA1c and cardiometabolic risk factors compared with medical management, with emergent differences over 1 year. Both treatments improve general quality-of-life measures, but RYGB provides greater improvement in the effect of weight on quality of life. These differences may help inform therapeutic decisions for diabetes and weight loss strategies in obese patients with type 2 diabetes until larger randomized trials are performed. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01073020.

DIET AND EXERCISE IN TYPE 2 DIABETES MELLITUS

The question is no longer whether diet and exercise can benefit the individual with type 2 diabetes. Rather, the type and duration of exercise the magnitude of the effects on glycemic control, insulin sensitivity, and on risk factors for cardiovascular disease must be considered in determining the feasibility and acceptability of an intervention program. It is now clear that regular physical exercise is important in both the prevention and treatment of type 2 diabetes. The benefits of exercise are many and include increased energy expenditure, which, combined with dietary restriction, leads to decreased body fat, increased insulin sensitivity, improved long-term glycemic control, improved lipid profiles, lower blood pressure, and increased cardiovascular fitness. Persons with type 2 diabetes often find it difficult to exercise and are at increased risk for injury or exacerbation of underlying diseases or diabetic complications. Therefore, before starting an exercise program, all patients with type 2 diabetes should have a complete history and physical examination, with particular attention to evaluation of cardiovascular disease, medications that may affect glycemic control during or after exercise, and diabetic complications including retinopathy, nephropathy, and neuropathy. Exercise programs should be designed to start slowly, build up gradually, and emphasize moderately intense exercise performed at least three times a week and preferably five to seven times a week for best results.

Diabetes medications and body weight

Tight diabetes control sometimes comes with a price: weight gain and hypoglycemia. Two of the three major recent trials that looked at the relationship between intensive diabetes control and cardiovascular events reported significant weight gain among the intensively treated groups. There is a growing concern that the weight gain induced by most diabetes medications diminishes their clinical benefits. On the other hand, there is a claim that treating diabetes with medications that are weight neutral or induces weight loss or less weight gain while minimizing those that increase body weight may emerge as the future direction for treating overweight and obese patients with diabetes. This review clarifies the weight effect of each of the currently available diabetes medications, and explains the mechanism of action behind this effect. Despite the great variability among reviewed clinical trials, the currently available evidence is quite sufficient to demonstrate the change in body weight in association with most of the currently available medications. This review also provides some guidelines on using diabetes medications during weight management programs.

The Peroxisome Proliferator-Activated Receptor-γ Agonist Pioglitazone Represses Inflammation in a Peroxisome Proliferator-Activated Receptor-α–Dependent Manner In Vitro and In Vivo in Mice

OBJECTIVES Our aim was to investigate if the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone modulates inflammation through PPARalpha mechanisms. BACKGROUND The thiazolidinediones (TZDs) pioglitazone and rosiglitazone are insulin-sensitizing PPARgamma agonists used to treat type 2 diabetes (T2DM). Despite evidence for TZDs limiting inflammation and atherosclerosis, questions exist regarding differential responses to TZDs. In a double-blinded, placebo-controlled 16-week trial among recently diagnosed T2DM subjects (n = 34), pioglitazone-treated subjects manifested lower triglycerides and lacked the increase in soluble vascular cell adhesion molecules (sVCAM)-1 evident in the placebo group. Previously we reported PPARalpha but not PPARgamma agonists could repress VCAM-1 expression. Since both triglyceride-lowering and VCAM-1 repression characterize PPARalpha activation, we studied pioglitazones effects via PPARalpha. METHODS Pioglitazone effects on known PPARalpha responses--ligand binding domain activation and PPARalpha target gene expression--were tested in vitro and in vivo, including in wild-type and PPARalpha-deficient cells and mice, and compared with the effects of other PPARgamma (rosiglitazone) and PPARalpha (WY14643) agonists. RESULTS Pioglitazone repressed endothelial TNFalpha-induced VCAM-1 messenger ribonucleic acid expression and promoter activity, and induced hepatic IkappaBalpha in a manner dependent on both pioglitazone exposure and PPARalpha expression. Pioglitazone also activated the PPARalpha ligand binding domain and induced PPARalpha target gene expression, with in vitro effects that were most pronounced in endothelial cells. In vivo, pioglitazone administration modulated sVCAM-1 levels and IkappaBalpha expression in wild-type but not PPARalpha-deficient mice. CONCLUSIONS Pioglitazone regulates inflammatory target genes in hepatic (IkappaBalpha) and endothelial (VCAM-1) settings in a PPARalpha-dependent manner. These data offer novel mechanisms that may underlie distinct TZD responses.

Two styles of acupuncture for treating painful diabetic neuropathy--a pilot randomised control trial.

In a pilot study, we evaluated the clinical and mechanistic effects of two styles of acupuncture, Traditional Chinese Medicine (TCM) and Japanese acupuncture, for the treatment of painful diabetic neuropathy. Out of seven patients enrolled, three received Traditional Chinese acupuncture while four received Japanese style acupuncture. Treatments were delivered once a week for 10 weeks. Acupuncturists were permitted to select the needle interventions. Substantial differences in diagnostic techniques, choice of acupuncture points, and needle manipulation were observed between TCM and Japanese acupuncturists. Clinically, patients allocated to Japanese acupuncture reported decreased neuropathy-associated pain according to the daily pain severity score, while the group allocated to the TCM acupuncture reported minimal effects. Both acupuncture styles, however, lowered pain according to the McGill Short Form Pain Score. The TCM style improved nerve sensation according to quantitative sensory testing while the Japanese style had a more equivocal effect. No evident changes were observed in glucose control or heart rate variability in either group.

Adiponectin and leptin in relation to insulin sensitivity.

An increased amount of adipose tissue or its disproportionate distribution between central and peripheral body regions is related to the development of insulin resistance, type 2 diabetes mellitus, dyslipidemia, atherosclerosis, and coronary artery disease. Until recently, adipose tissue was regarded as a storage depot for lipids. It is now viewed as a hormonally active organ that plays a crucial metabolic role. The most important products of adipose tissue collectively referred to as adipocytokines, include adiponectin, leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), resistin, plasminogen-activating inhibitor-I (PAI-1), and angiotensinogen. These low and medium molecular weight proteins play an important role in the adipose tissue physiology and are believed to be a link between obesity, insulin resistance and endothelial dysfunction. This review describes the metabolic role of two of these proteins, adiponectin and leptin, in relation to insulin sensitivity.

Adjustable Gastric Band Surgery or Medical Management in Patients With Type 2 Diabetes: A Randomized Clinical Trial

CONTEXT Recommendations for surgical, compared with lifestyle and pharmacologically based, approaches for type 2 diabetes (T2D) management remain controversial. OBJECTIVE The objective was to compare laparoscopic adjustable gastric band (LAGB) to an intensive medical diabetes and weight management (IMWM) program for T2D. DESIGN This was designed as a prospective, randomized clinical trial. SETTING The setting was two Harvard Medical School-affiliated academic institutions. INTERVENTIONS AND PARTICIPANTS: A 12-month randomized trial comparing LAGB (n = 23) vs IMWM (n = 22) in persons aged 21-65 years with body mass index of 30-45 kg/m(2), T2D diagnosed more than 1 year earlier, and glycated hemoglobin (HbA(1c)) ≥ 6.5% on antihyperglycemic medication(s). MAIN OUTCOME MEASURE The proportion meeting the prespecified primary glycemic endpoint, defined as HbA(1c) < 6.5% and fasting glucose < 7.0 mmol/L at 12 months, on or off medication. RESULTS After randomization, five participants did not undergo the surgical intervention. Of the 40 initiating intervention (22 males/18 females; age, 51 ± 10 y; body mass index, 36.5 ± 3.7 kg/m(2); diabetes duration, 9 ± 5 y; HbA(1c), 8.2 ± 1.2%; 40% on insulin), the proportion meeting the primary glycemic endpoint was achieved in 33% of the LAGB patients and 23% of the IMWM patients (P = .457). HbA(1c) reduction was similar between groups at both 3 and 12 months (-1.2 ± 0.3 vs -1.0 ± 0.3%; P = .496). Weight loss was similar at 3 months but greater 12 months after LAGB (-13.5 ± 1.7 vs -8.5 ± 1.6 kg; P = .027). Systolic blood pressure reduction was greater after IMWM than LAGB, whereas changes in diastolic blood pressure, lipids, fitness, and cardiovascular risk scores were similar between groups. Patient-reported health status, assessed using the Short Form-36, Impact of Weight on Quality of Life, and Problem Areas in Diabetes, all improved similarly between groups. CONCLUSIONS LAGB and a multidisciplinary IMWM program have similar 1-year benefits on diabetes control, cardiometabolic risk, and patient satisfaction, which should be considered in the context of other factors, such as personal preference, when selecting treatment options with obese T2D patients. Longer duration studies are important to understand emergent differences.

Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care

Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports.

Lifestyle modification and endothelial function in obese subjects

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-α, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.