Nutritional management of type 2 diabetes in subjects with obesity: an international guideline for clinical practice.

Type 2 diabetes mellitus (T2DM) and obesity represent a global public health problem. Current nutritional recommendations focused on weight loss and overall dietary quality. However, there is no consensus on the optimal macronutrient composition of the diet, particularly for the long-term management of T2DM in subjects with obesity. An international panel of experts reviewed and critically appraised the updated literature published on the topic. This review primarily examines the evidence for areas of consensus and uncertainty about nutritional therapy in patients with T2DM and obesity. The aim of this article is to provide nutritional advice to manage these patients in clinical practice.

Nutritional guidelines for the management of insulin resistance.

Obesity and its related co-morbidities, namely type 2 diabetes (T2D), pose a significant global public health problem. Insulin resistance (IR) in muscle and liver is the core pathophysiologic defect that underlies obesity preceding and predicting the onset of T2D in susceptible humans. There is a broad population with IR that has no indication for prescription of medications, who still need medical consultation and specific advice in this respect. This prevalent need can be achieved by appropriate diet, exercise, and other behavioral therapies for lifestyle interventions. Despite a well-recognized role of IR in the progression to metabolic diseases, no specific nutritional recommendations exist to manage this condition, to the best of our knowledge. An international panel of experts reviewed and critically appraised the updated literature published about this topic. This review primarily examines the evidence for areas of consensus and ongoing uncertainty or controversy about diet and exercise approaches for IR. The aim of this article is to present the most common IR states, namely obesity and Polycystic Ovary Syndrome (PCOS), and provide nutritional advice to manage IR, hyperinsulinemia, and reactive hypoglycemia. These nutritional guidelines could prevent progression or worsening of IR with resultant beta-cell failure and, as a result, T2D.

Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus.

In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, on hepatic glucose production (HGP), plasma glucose and free fatty acid (FFA) concentrations. 11 T2D (Type 2 Diabetes) subjects (age = 53 ± 3 years) were studied at baseline (BAS) and after 16-weeks of Exubera® treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3H-glucose); oral glucose tolerance test (OGTT); and a 24-h plasma glucose (24-h PG) profile. At end of study (EOS) we observed a significant decrease in fasting plasma glucose (FPG, 215 ± 15 to 137 ± 11 mg/dl), 2-hour plasma glucose (2-h PG, 309 ± 9 to 264 ± 11 mg/dl), glycated hemoglobin (HbA1c, 10.3 ± 0.5% to 7.5 ± 0.3%,), mean 24-h PG profile (212 ± 17 to 141 ± 8 mg/dl), FFA fasting (665 ± 106 to 479 ± 61 µM), post-OGTT (433 ± 83 to 239 ± 28 µM), and triglyceride (213 ± 39 to 120 ± 14 mg/dl), while high density cholesterol (HDL-C) increased (35 ± 3 to 47 ± 9 mg/dl). The basal HGP decreased significantly and the insulin secretion/insulin resistance (disposition) index increased significantly. There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera® we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.

Pleiotropic effects of thiazolidinediones: implications for the treatment of patients with type 2 diabetes mellitus.

Thiazolidinediones (TZDs) are insulin-sensitizing antidiabetes agents that act through the peroxisome proliferator-activated receptor-γ to cause a durable improvement in glycemic control in patients with type 2 diabetes mellitus. Although less well recognized, TZDs also exert a protective effect on ß-cell function. In addition to their beneficial effects on glucose homeostasis, TZDs-especially pioglitazone-exert a number of other pleiotropic effects that make them ideal agents as monotherapy or in combination with other oral agents, glucagon-like peptide-1 analogs, or insulin. Pioglitazone improves endothelial dysfunction, reduces blood pressure, corrects diabetic dyslipidemia, and reduces circulating levels of inflammatory cytokines and prothrombotic factors. Pioglitazone also redistributes fat and toxic lipid metabolites in muscle, liver, ß cells, and arteries, and deposits the fat in subcutaneous adipocytes where it cannot exert its lipotoxic effects. Consistent with these antiatherogenic effects, pioglitazone reduced major adverse cardiac event endpoints (ie, mortality, myocardial infarction, and stroke) in the Prospective Pioglitazone Clinical Trial in Macrovascular Events and in a meta-analysis of all other published pioglitazone trials. Pioglitazone also mobilizes fat out of the liver, improving liver function and histologic abnormalities in patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Pioglitazone also reduces proteinuria, all-cause mortality, and cardiovascular events in patients with type 2 diabetes mellitus with a reduced glomerular filtration rate. These benefits must be weighed against the side effects of the drug, including weight gain, fluid retention, atypical fractures, and, possibly, bladder cancer. When low doses of pioglitazone are used (eg, 7.5-30 mg/d) with gradual titration, and physician recognition of the potential side effects are applied, the risk-to-benefit ratio is very favorable. Despite having similar effects on glycemic control, pioglitazone and rosiglitazone appear to have different effects on cardiovascular outcomes. Rosiglitazone has been associated with an increased risk of myocardial infarction, and its use in the United States is restricted because of cardiovascular safety concerns.

New-onset diabetes mellitus: predictive factors and impact on the outcome of patients undergoing liver transplantation.

Liver transplantation (LT) for hepatocellular carcinoma (HCC) is the treatment of choice for patients with tumor characteristics within the Milan criteria associated with Child B or C cirrhosis. LT provides the best cure for both the tumor and the cirrhosis. There have been several emerging reports that new-onset diabetes mellitus (NODM) after transplantation (NODAT) is one of the most negative predictive factors for low survival rate and related co-morbidities. Little is known about the onset of NODM in post-transplant patients and, overall, whether the pathogenesis of NODM differs from that known for the general population. Principally, it is still unknown whether NODAT is related to the primary hepatic disease, the surgical procedures, immunosuppressive treatments, or is it due to the donor liver. This review will focus on the identification of factors, in the setting of LT, which may lead to the development of NODM. Early prevention of these factors may abate the incidence of NODM and positively impact survival rate, and thus ameliorate the worsening of cardiovascular risk factors which usually occur after LT.