Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been introduced as a new class of anti-diabetic agents. In addition to their glycemic action, SGLT2 inhibitors also have a number of non-glycemic effects that may contribute to renal and/or cardiovascular benefits. These include effects on tubuloglomerular feedback in the kidney, body weight, blood pressure, and serum uric acid. Other non-glycemic effects of SGLT2 inhibitors that need to be further studied include the effects on lipid profiles, food intake, and secretion of hormones such as leptin, incretins, and aldosterone. Also, the exact mechanisms of various non-glycemic actions should be further studied. Additionally, SGLT2 inhibitor therapy in combination with other drugs may have beneficial glycemic and non-glycemic effects.
Aldosterone ; Blood Pressure ; Body Weight ; Diabetes Mellitus ; Eating ; Glucose ; Incretins ; Kidney ; Leptin ; Sodium ; Uric Acid

BACKGROUND: We examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) on insulin secretion in women with previous gestational diabetes (pGDM). METHODS: A 75-g oral glucose tolerance test (OGTT) was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured. RESULTS: Among 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT) and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT. CONCLUSION: GLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes.
Biomarkers ; Blood Glucose ; Diabetes, Gestational ; Female ; Glucagon ; Glucagon-Like Peptide 1 ; Glucose ; Glucose Tolerance Test ; Heredity ; Humans ; Incretins ; Insulin ; Pregnancy

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.
Animals ; Blood Glucose ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Humans ; Hypoglycemic Agents ; Incretins ; Insulin Resistance ; Korea ; Treatment Outcome

Individuals who have diabetes should receive individualized medical nutrition therapy (MNT) based on an assessment of the individual's current eating patterns, preferences, and metabolic goals. The dietician should be able to coordinate food choices with the type of diabetes medicine being taken. Knowledge of the actions, side effects, and contraindication of diabetes medicine can help the dietician coordinate appropriate MNT and physical activity, to assist the individual with diabetes to achieve optimal glycemic control without unwanted effects. Carbohydrate consistency is important for diabetic patients on oral diabetes medications. The primary side effects with initial treatment of biguanides, alpha-glucosidase inhibitors, and incretin mimetics include gastrointestinal discomfort, which can be minimized by taking the medication with food, starting at a low dosage, and increasing the dosage slowly. Common side effects from use of insulin and insulin secretagogues (sulfonylureas and meglitinides) are hypoglycemia and weight gain. Consistent meal times and carbohydrate consistency are important to reduce risk of hypoglycemia. Energy restriction, reduced fat intake, regular physical activity, and avoidance of frequent hypoglycemia can be beneficial in preventing or limiting weight gain. The insulin regimen should be fitted to the meal plan and adjusted over time based on the results of blood glucose monitoring.
alpha-Glucosidases ; Biguanides ; Blood Glucose ; Diabetes Mellitus ; Eating ; Humans ; Hypoglycemia ; Incretins ; Insulin ; Meals ; Motor Activity ; Nutrition Therapy ; Nutritionists ; Weight Gain

Bone disease is a serious complication to diabetes. Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) suffer from an increased risk of fracture, most notably at the hip, compared with patients without diabetes. Confounders such as patient sex, age, body mass index, blood glucose status, fall risk, and diabetes medications may influence the fracture risk. Different underlying mechanisms contribute to bone disease in patients with diabetes. Bone quality is affected by low bone turnover in T1D and T2D, and furthermore, incorporation of advanced glycation end-products, changes in the incretin hormone response, and microvascular complications contribute to impaired bone quality and increased fracture risk. Diagnosis of bone disease in patients with diabetes is a challenge as current methods for fracture prediction such as bone mineral density T-score and fracture risk assessment tools underestimate fracture risk for patients with T1D and T2D. This review focuses on bone disease and fracture risk in patients with diabetes regarding epidemiology, underlying disease mechanisms, and diagnostic methods, and we also provide considerations regarding the management of diabetes patients with bone disease in terms of an intervention threshold and different treatments.
Blood Glucose ; Body Mass Index ; Bone Density ; Bone Diseases ; Bone Remodeling ; Diagnosis ; Epidemiology ; Hip ; Humans ; Incretins ; Osteoporosis ; Risk Assessment

The majority of people diagnosed with diabetes mellitus are in the working age group in developing countries. The interrelationship of diabetes and work, that is, diabetes affecting work and work affecting diabetes, becomes an important issue for these people. Therapeutic options for the diabetic worker have been developed, and currently include various insulins, insulin sensitizers and secretagogues, incretin mimetics and enhancers, and alpha glucosidase inhibitors. Hypoglycemia and hypoglycaemic unawareness are important and unwanted treatment side effects. The risk they pose with respect to cognitive impairment can have safety implications. The understanding of the therapeutic options in the management of diabetic workers, blood glucose awareness training, and self-monitoring blood glucose will help to mitigate this risk. Employment decisions must also take into account the extent to which the jobs performed by the worker are safety sensitive. A risk assessment matrix, based on the extent to which a job is considered safety sensitive and based on the severity of the hypoglycaemia, may assist in determining one's fitness to work. Support at the workplace, such as a provision of healthy food options and arrangements for affected workers will be helpful for such workers. Arrangements include permission to carry and consume emergency sugar, flexible meal times, self-monitoring blood glucose when required, storage/disposal facilities for medicine such as insulin and needles, time off for medical appointments, and structured self-help programs.
alpha-Glucosidases ; Appointments and Schedules ; Blood Glucose ; Developing Countries ; Diabetes Mellitus ; Emergencies ; Employment ; Humans ; Hypoglycemia ; Incretins ; Insulin ; Insulins ; Meals ; Needles ; Risk Assessment

Type 2 diabetes mellitus (T2DM) is a progressive disorder caused by a combination of insulin resistance and betacell dysfunction. The role of new hormones and systems in maintaining blood glucose homeostasis has recently been recognized. This recognition has led to the development of several novel classes of medications, including the incretin mimetic agents (glucagon like polypeptide-1 analogs and dipeptidyl peptidase IV inhibitors), the amylin analog and the endocannabinoid-1 receptor blocker. This review looks at these new agents in terms of their mode of action, pharmacokinetics and use in clinical practice. The new agents offer treatment options in select adult patients now, however, the efficacy and the safety has to be evaluated thoroughly by long term studies before the application to pediatric patients.
Adult ; Blood Glucose ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptides ; Homeostasis ; Humans ; Incretins ; Insulin Resistance ; Islet Amyloid Polypeptide

Nonalcoholic fatty liver disease (NAFLD) is more prevalent in diabetic patients than in non-diabetic subjects, because the two diseases share a common pathophysiological mechanism. Associated abnormalities can be observed from the pre-diabetic stage. Lifestyle intervention, including diet, exercise, and weight loss, is the primary recommended therapy for NAFLD. Among the therapeutic drugs for NAFLD treatment, anti-diabetic agents are aimed at improving or slowing the progression of NAFLD in addition to lowering blood glucose. In this paper, we systemically review the evidence surrounding antidiabetic medications and their ability to improve disease progression in patients with NAFLD.
Blood Glucose ; Diabetes Mellitus ; Diet ; Disease Progression ; Humans ; Incretins ; Life Style ; Non-alcoholic Fatty Liver Disease* ; Sodium-Glucose Transporter 2 ; Thiazolidinediones ; Weight Loss

The incretin hormones glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have recently received much attention for their roles in type 2 diabetes therapy. GLP-1 stimulated insulin secretion in a glucose-dependent manner and is secreted by intestinal L cells. It also regulates blood glucose concentration, stomach motility, appetite, and body weight. These actions are mediated through G-protein-coupled receptors highly expressed on pancreatic beta cells and also exert indirect metabolic actions. Activation of GLP-1 receptors also produces nonglycemic effects in various tissues. The pleiotropic effects of GLP-1 have been recently reported. The mechanisms identified in preclinical studies have potential translational relevance for the treatment of disease. Here, the nonglycemic effects of GLP-1, especially those on the liver, central nervous system, and bone, were reviewed.
Appetite ; Blood Glucose ; Body Weight ; Central Nervous System ; Enteroendocrine Cells ; Glucagon ; Glucagon-Like Peptide 1 ; Incretins ; Insulin ; Insulin-Secreting Cells ; Liver ; Receptors, G-Protein-Coupled ; Stomach

The increasing risk of glucose intolerance and diabetes associated with aging is well established. However, it is difficult to determine whether changes in glucose metabolism result from biological aging itself or due to various environmental factors that occur during the aging process. Many epidemiologic studies have shown that plasma glucose levels after oral glucose tolerance test rise consecutively for every decade of age, but many of these studies also demonstrated the effects of environmental factors including obesity and exercise. In some studies, the development of insulin resistance and insulin secretion defects due to biological aging itself have also been identified as major etiologic factors of glucose intolerance. However, the rate of diabetes development due to these factors is expected to be very slow and largely preventable by addressing environmental risk factors.
Aging ; Blood Glucose ; Carbohydrate Metabolism ; Epidemiologic Studies ; Glucose Intolerance ; Glucose Tolerance Test ; Glucose ; Incretins ; Insulin ; Insulin Resistance ; Metabolism ; Obesity ; Risk Factors