Diabetic peripheral neuropathy in type 2 diabetes mellitus in Korea

Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients.     

The clinical and immunogenetic characteristics of adult-onset type 1 diabetes mellitus in Korea

Although the HLA class II alleles and immunological abnormalities are associated with type 1 diabetes mellitus (T1DM) in all racial groups, there are considerable variations in the genotypes and the prevalence of autoantibodies. In order to investigate the characteristics of the immunogenetic patterns and to use these as an early diagnostic tool and guideline for a therapeutic plan, we examined the clinical characteristics and the patterns of anti-GAD antibody (GADA), IA-2 antibody (IA-2A), HLA-DR and HLA-DQ in Korean adult-onset T1DM patients. Adult-onset patients had higher serum C-peptide levels than child-onset patients. In adult-onset patients, the prevalence of GADA and IA-2A were 59.5% and 15.3% respectively, and increased frequencies of HLADR4 and-DR9 were found. The frequencies of HLADQA1,-DQB1 and-DQ heterodimers were similar to those of the control, but child-onset patients had high frequencies of the HLA-DR3,-DR4,-DR9, DQA1*0301, DQA1*0501 and DQB1*0201 genotypes. In conclusion, Korean adult-onset T1DM patients had a lower prevalence of GADA, which was comparable to that found in Caucasian patients. The detection of GADA might help to predict the insulin dependency of adult-onset diabetes. Difference in the frequencies of diabetes associated with HLA type suggests that there might be a heterogeneity in the pathogenesis of diabetes according to the age of onset.     

Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea

In the presence of obesity, beta-cell mass needs to be increased to compensate for the accompanying demands and maintain euglycemia. However, in Korea, the majority of type 2 diabetic patients are nonobese. We determined the absolute masses, relative volumes, and ratio of alpha- and beta-cell in the pancreas and islets in normal and diabetic Korean subjects to correlate these findings with the clinical characteristics. Whole pancreases procured from organ donors were divided into 24 parts (control 1, n = 9). Tissue was also obtained by surgical resection after 35 partial pancreatectomies: in 25 diabetic patients, 10 age- and body mass index (BMI)-matched patients of benign or malignant pancreatic tumor without diabetes mellitus (DM) (control 2). Morphometric quantifications were performed. In control 1, the relative volume of beta-cells was 2.1 +/- 0.9%, and the total beta-cell mass was 1.3 +/- 0.3 g. The relative volume of beta-cells was found to be variable (control 1, 2.1 +/- 0.9%; control 2, 1.9 +/- 0.7%; DM, 1.4 +/- 1.0%; P < 0.05 DM vs. control 1 and 2) and showed good correlation with BMI (control 1, r(2) = 0.64; DM, r(2) = 0.55; all subjects, r(2) = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of alpha-cell area to beta-cell area in the islet was higher than in control 1 and 2 (0.81 +/- 0.4 vs. 0.29 +/- 0.2, 0.20 +/- 0.1, P < 0.05). Additionally, significant alpha-cell expansion and a decreased beta-cell fraction were predominantly observed in larger islets (islet area, >6415 micro m(2); P < 0.05) in control 1 and diabetic patients. The relative volume of beta-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased beta-cell but increased alpha-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes.     

Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum

To determine the prevalence of glucose intolerance in Korean women with gestational diabetes mellitus (GDM) between 6 and 8 weeks postpartum and identify which antepartum variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT), we prospectively performed 75 g oral glucose tolerance test (OGTT) between 6 and 8 weeks postpartum in women with GDM. WHO criteria were used for classification of glucose tolerance postpartum. Of 392 women with GDM were detected during the study period, 311 women participated in this study. Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Multiple logistic regression analysis revealed that pre-pregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT were independently associated with postpartum diabetes. Pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were independently associated with postpartum IGT. Our results support the importance of postpartum testing in Korean women with GDM, and demonstrated that impaired beta-cell function and pre-pregnancy obesity were associated with glucose intolerance at early postpartum.     

Macroangiopathy in diabetes mellitus

In patients with diabetic angiopathy until today, no histological nor histochemical evidence has been found to define a specific type of diabetic arteriopathy. Consequently, diabetic arteriosclerosis is considered as a more serious form of atherosclerosis characterized by its premature onset. Hyperglycemia is assumed to be the crucial pathophysiological cause of the development of macro- and microangiopathy in diabetes mellitus. Apparently, hyperglycemia has a direct toxic influence on the arterial wall by increased accumulation of irreversible glycosylation end products, and secondly, it provokes endothelial dysfunction. The frequently occurring ulcerations of the diabetic foot are primarily caused by neuropathy; however, peripheral vascular disease (PVD) is often associated. The risk of suffering from PVD in diabetic patients is approximately four-fold. Usually, the distal segments of the lower leg arteries are concerned, where reconstructive intervention is complicated or even impossible. Diabetes is considered as an independent risk factor for cardio- and cerebrovascular diseases with almost twice as high rates for recurrent myocardial infarction, and a 3.7 fold higher relative risk for stroke in diabetic, compared to non-diabetic patients. This review looks at the correlations between hyperglycemia and arteriosclerosis, but also the treatment options in diabetic patients. Until now, there is no evidence for an association between an optimal control of blood glucose levels and a decrease in the risk of coronary heart disease, stroke, or PVD. In contrast, an attenuation of microvascular lesions is achieved by stringent control of blood glucose levels. Thus, although the development of macroangiopathy may not be significantly influenced, the conduction of a stringent control regimen of plasmatic glucose levels is advisable.     

Bacteriuria in diabetes mellitus

Summary One hundred and four diabetic patients with bacteriuria were followed for a mean period of 44 months. They were divided in two groups cured and persistent according to the results of treatment. Retinopathy and albuminuria as evidences of microangiopathy were present at the beginning of the study in a greater number of patients and in a greater degree in those with persistent bacteriuria than in those cured. At follow-up the number of patients with and the severity of retinopathy and albuminuria were higher in those with persistent bacteriuria although not statistically different. Microangiopathy usually antedated bacteriuria and may have contributed to its persistence, although the possibility that bacteriuria played a role in the progression of microangiopathy cannot be excluded. No significant deterioration in renal function became apparent in either group, suggesting that persistent bacteriuria had not obviously contributed, to the development of pyelonephritis or progressive renal damage.Presented in part at the 29^th Annual Meeting of the American Diabetes Association in New York, N.Y. June 29^th 1969.     

Hyperkalemia in diabetes mellitus

Potassium filtered at the glomerulus is almost completely reabsorbed before the distal tubule; it must therefore be secreted into the collecting duct. The rate of potassium secretion is determined by a number of factors, notably aldosterone, distal sodium delivery, and serum potassium. Normal serum potassium is maintained by the interplay of passive leak of potassium from the cells and its active return to the cells. Transmembrane potassium distribution is influenced largely by acid-base equilibrium and hormones including insulin and catecholamines. In the diabetic with ketoacidosis hyperkalemia, in the face of potassium depletion, is attributable to reduced renal function, acidosis, release of potassium from cells due to glycogenolysis, and lack of insulin. Chronic hyperkalemia in diabetics is most often attributable to hyporeninemic hypoaldosteronism but other conditions including urinary tract obstruction may also contribute. A variety of clinical situations (e.g., volume depletion) and drugs (e.g., nonsteroidal antiinflammatory agents, and heparin) may acutely provoke hyperkalemia in susceptible individuals.     

Fibromyalgia in diabetes mellitus

OBJECTIVE: The aim of this study was to evaluate the prevalence of fibromyalgia (FM) in patients with diabetes mellitus (DM). SUBJECTS: The study included 100 consecutive unselected patients with DM attending our diabetes clinic. Patients were divided into two groups: 45 patients with type 1 diabetes and 55 patients with type 2 diabetes. A group of 50 healthy hospital staff members served as controls. The FM was diagnosed according to the 1990 American College of Rheumatology criteria. Counts of 18 tender points were performed by thumb palpation and assessed by dolorimeter. Routine biochemical tests and levels of HbA(1c) were recorded in each patient. RESULTS: The main outcome measure was the association of FM with DM. Fibromyalgia was diagnosed in 17 patients (17%) with DM and in only one (2%) healthy control ( P=0.008). No differences in patients were noted in the prevalence of FM between type 1 and type 2 diabetes (18.5% vs 15.5%, respectively). Patients with both FM and DM had significantly higher levels of HbA(1c) than DM patients without FM (9.2+/-1.1% vs 6.4+/-1.5%) ( P<0.05). Similarly, the numbers of tender points, pain scores, and the prevalence of sleep disturbances, fatigue, and headaches were higher in this group of patients. A significant correlation was observed between the numbers of tender points and HbA(1c) levels in the DM patients with FM ( r=0.72, P=0.027). CONCLUSION: Fibromyalgia is a common finding in patients with types 1 and 2 diabetes, and its prevalence could be related to control of the disease. As with other diabetes complications, FM might be prevented by improved control of blood glucose levels.     

Magnesium in diabetes mellitus

A tendency for magnesium deficiency in patients with diabetes mellitus is well-established. Glucosuria-related hypermagnesiuria, nutritional factors and hyperinsulinaemia-related hypermagnesiuria all can contribute. The plasma magnesium level has been shown to be inversely related to insulin sensitivity. Magnesium supplementation improves insulin sensitivity as well as insulin secretion in patients with type 2 diabetes. Nevertheless, no beneficial effects of oral magnesium supplementation has been demonstrated on glycaemic control either in patients with diabetes type 1 or 2. Oral magnesium supplementation reduced the development of type 2 diabetes in predisposed rats. There are some indications that magnesium decreases blood pressure, but negative results have been observed in trials that were, however, not designed to test effect on blood pressure as primary parameter. Patients with (severe) retinopathy have a lower plasma magnesium level compared to patients without retinopathy and a prospective study has shown the plasma magnesium level to be inversely related to occurrence or progression of retinopathy. Further study on magnesium (supplementation) is warranted in the prevention of type 2 and of (progression of) retinopathy as well as a means to reduce high blood pressure.     

Hypertension in diabetes mellitus

Hypertension, commonly associated with diabetes mellitus, plays a major role in the severity and progression of diabetic complications. The frequency and impact of hypertension on the course of diabetic nephropathy, and the role of persistent microalbuminuria either as a predictor of future overt diabetic nephropathy or as a marker of incipient hypertension is reviewed. The special considerations for antihypertensive agents in diabetes as well as the rationale for early intervention using a "substitution" rather than "stepped-care" approach are discussed.     

Nephroprotection in diabetes mellitus

Present study analyses nephroprotective effect of various therapeutic interventions at different stages of kidney involvement in diabetes mellitus. A MEDLINE search of past 10 years data on various experimental studies, controlled clinical trials, meta-analysis and editorials pertaining to nephroprotection in diabetes mellitus was made. Effect of various therapeutic interventions such as metabolic glycaemic control, restricted protein diet and antihypertensive drugs (especially ACE inhibitors) has been analysed on the progression of different stages of kidney involvement in diabetes mellitus such as normoalbuminuria, microalbuminuria, diabetic nephropathy and end stage renal disease (ESRD). An attempt has been made to analyse differential long-term impact of various therapeutic interventions in relation to type of diabetes mellitus (i.e., IDDM and NIDDM) and associated hypertension. Progression of IDDM patients having microalbuminuria or diabetic nephropathy with or without hypertension has improved during the past decade largely because of adequate glycaemic control and effective antihypertensive treatment with conventional drugs e.g. beta-blockers and calcium antagonists, and more so due to the use of ACE inhibitors e.g. captopril, enalapril etc. Superiority of ACE inhibitor tends to decline from normotensive stage to the degree of rise in systemic blood pressure. However, data in NIDDM patients suffering from diabetic nephropathy is incomplete and inconclusive.