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 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

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

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

Glucagon like peptide-1 (GLP-1) is an intestinal L cell derived incretin hormone which stimulates insulin secretion of beta cell and inhibits glucagon secretion of alpha cell of pancreatic islets. GLP-1 receptors are located in pancreas as well as in a wide variety of tissue such as gastrointestinal tract, heart, blood vessel, lung, brain, kidney, and bone. Therefore GLP-1 and GLP-1 based treatment have multiple extrapancreatic effects which are inhibition of gastrointestinal motility, reduction of appetite, weight loss, increase of cardiac output, cardiovascular protection, neuroprotection, renoprotection, and increase of bone mineral density. Recently, besides GLP-1 receptor dependent pathway, GLP-1 receptor independent pathway has been identified in the extrapancreatic effect of GLP-1 in liver, adipose tissue, muscle, cardiovascular system. This review provides an overview of the pleiotropic effect of GLP-1 in the extrapancreatic organ through review of animal and clinical research.
Adipose Tissue ; Animals ; Appetite ; Blood Vessels ; Bone Density ; Brain ; Cardiac Output ; Cardiovascular System ; Enteroendocrine Cells ; Gastrointestinal Motility ; Gastrointestinal Tract ; Glucagon* ; Glucagon-Like Peptide 1 ; Heart ; Incretins ; Insulin ; Islets of Langerhans ; Kidney ; Liver ; Lung ; Pancreas ; Weight Loss ; Glucagon-Like Peptide-1 Receptor

The incretin effect, which is a unique stimulus of insulin secretion in response to oral ingestion of nutrients, is calculated by the difference in insulin secretory responses from an oral glucose tolerance test (OGTT) and a corresponding isoglycemic intravenous glucose infusion (IIGI) study. The OGTT model of this study, which is individualized by fitting the glucose profiles during an OGTT, was developed to predict the glucose profile during an IIGI study in the same subject. Also, the model predicts the insulin and incretin profiles during both studies. The incretin effect, estimated by simulation, was compared with that measured by physiologic studies from eight human subjects with normal glucose tolerance, and the result exhibited a good correlation (r > 0.8); the incretin effect from the simulation was 56.5% +/- 10.6% while the one from the measured data was 52.5% +/- 19.6%. In conclusion, the parameters of the OGTT model have been successfully estimated to predict the profiles of both OGTTs and IIGI studies. Therefore, with glucose data from the OGTT alone, this model could control and predict the physiologic responses, including insulin secretion during OGTTs and IIGI studies, which could eventually eliminate the need for complex and cumbersome IIGI studies in incretin research.
Administration, Oral ; Adult ; Area Under Curve ; Blood Glucose/analysis ; *Computer Simulation ; Female ; Glucose/metabolism/pharmacology ; Glucose Tolerance Test ; Humans ; Incretins/*blood ; Insulin/blood ; Liver/drug effects ; Middle Aged ; *Models, Theoretical ; ROC Curve

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

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: Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to reduce blood glucose in type 2 diabetes by prolonging the activity of circulating incretins. However, the factors that affect the efficacy of sitagliptin have not yet been demonstrated. Therefore, we studied them in a Korean population. METHODS: We performed a retrospective analysis in patients taking sitagliptin in Wonju Christian Hospital. One hundred-fifty patients whose serum HbA1c ranged from 6.5% to 11% participated in this study. These patients were divided into two groups: responder and non-responder. The responder group consisted of subjects with glucose lowering greater than 5% of baseline HbA1c. The others were in non-responder group. We analyzed anthropometric data and biochemical markers in all groups, then compared responder group and non-responder group by logistic regression. RESULTS: The change in HbA1c level across all groups was 8.25 +/- 0.82% to 7.64 +/- 1.03% (P value = 0.000). There were 93 and 57 patients in responder and non-responder group, respectively. The responder group had lower BMI, body fat (kg), body fat (%) than the non-responder group (P value = 0.024, P value = 0.029, P value = 0.025), and the HbA1c lowering effect of sitagliptin was greater in male than female (P value = 0.000). CONCLUSION: In this study, HbA1c was effectively lowered in 62% of the patients. The factors that affect the efficacy of sitagliptin were BMI, body fat (kg) body fat (%), and sex. Based on these results, we conclude that sitagliptin lowers glucose more effectively in non-obese male patients.
Adipose Tissue ; Biomarkers ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors ; Female ; Glucose ; Humans ; Incretins ; Kangwon-do ; Logistic Models ; Male ; Retrospective Studies ; Sitagliptin Phosphate

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