Microalbuminuria cannot predict cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus

In order to examine whether the existence of microalbuminuria can predict the development of overt proteinuria and cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus (NIDDM), we investigated 47 patients for a 10-year follow-up period. Patients were divided into two groups by the initial values of urinary albumin excretion rates. The percentage of patients who developed overt proteinuria during the follow-up period was significantly higher in patients who were initially classified as microalbuminuric group (63.6%) than in normoalbuminuric group (17.4%). During the follow-up period, one of the patients with normoalbuminuria had died of congestive heart failure, while four of those with microalbuminuria had died; one of stroke and three from noncardiovascular diseases. These results indicate that the existence of microalbuminuria had the predictive power for the development of overt proteinuria, but not for cardiovascular death in Japanese subjects with NIDDM.     

Hepatocyte nuclear factor-1a gene and non-insulin-dependent diabetes mellitus in the Japanese population

Recently, hepatocyte nuclear factor-1α (HNF-1α, which is encoded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3). We studied the contribution of TCF1 to genetic susceptibility to common non-insulin-dependent diabetes mellitus (type 2) in Japanese subjects by investigating allelic association with type 2 diabetes use of three markers. We also studied the frequency of the G191D mutation, the only mutation of TCF1 reported so far in late-onset type 2 diabetes. A total of 356 subjects were studied. There were no significant differences in allele frequency of the three markers between patients with type 2 diabetes and control subjects. A G191D mutation was not found in the subjects studied, giving a frequency of less than 0.4% in common type 2 diabetes. The lack of association of type 2 diabetes with three markers in and near TCF1 suggests that mutations in TCF1 derived from a limited number of founders are not a major cause of common type 2 diabetes even in the genetically homogeneous Japanese population. The data also indicate that the G191D mutation in TCF1 plays little, if any, role in susceptibility to common type 2 diabetes in the Japanese. Received: 28 March 1998 / Accepted in revised form: 24 June 1998     

Hypercalciuria and hematuria in non-insulin-dependent diabetes mellitus

This study was undertaken to examine whether patients with non-insulin-dependent diabetes (NIDDM) are hypercalciuric and whether there is a pathophysiologic relationship between urinary calcium excretion (UCE) and the degree of diabetic nephropathy. Although UCE did not parallel the increase of urinary albumin excretion rate (AER) and the presence of hematuria was not corrected with the degree of UCE, we confirmed that 36% of diabetic patients have hypercalciuria and that the prevalence of hypercalciuria is more frequent in diabetic patients with normo- or microalbuminuria than in the controls. In 6 months, the AER of two hypercalciuric patients increased. However, the blood pressure and HbA_1c of these two patients increased during the same 6 months. Therefore, it remains unclear whether hypercalciuria induced an increase in the AER of these patients.     

Renal complications in non-insulin-dependent diabetes mellitus

Renal failure among elderly individuals with diabetes is a substantial clinical and public health problem. These individuals account for the majority of renal failure among people with diabetes mellitus in the United States. Although limited population-based data directly provide evidence regarding the incidence of and risk factors for ESRD, extant data suggest that blacks and Pima Indians have a markedly increased risk of ESRD compared with whites in the United States. Proteinuria and microalbuminuria appear to be extremely common in elderly individuals with NIDDM and are strongly associated with overall survival, cardiovascular morbidity and mortality, and the development of ESRD. Although randomized clinical trials are needed to test intervention strategies to reduce morbidity and mortality associated with renal disease among individuals with NIDDM, extant data suggest that management efforts directed at hypertension control and, possibly, moderate restriction of protein intake may be important therapeutic modalities for prevention of renal disease and its associated sequelae among elderly individuals with diabetes.     

Microalbuminuria associated with a rise in blood pressure in non-insulin-dependent diabetes

The association between microalbuminuria and systemic blood pressure was investigated in 80 nonproteinuric subjects with non-insulin-dependent diabetes. Seventeen of 80 diabetics had urinary albumin excretion rates (AER) over 20 μg/min and were defined as microalbuminuric. The microalbuminuric diabetics showed a higher incidence of proliferative retinopathy and neuropathy than the normoalbuminurics. Moreover, the former group had significantly higher values of systolic blood pressure compared to the latter, although the creatinine clearance was not significantly different between the two groups. These results suggest that microalbuminuria is strongly associated with a rise of systemic blood pressure in non-insulin-dependent diabetics.     

Screening for non-insulin-dependent diabetes mellitus in the elderly

There are three major obstacles to a recommendation for screening the elderly for NIDDM. The first is the conflicting evidence as to whether early detection and treatment reduce complications. The second is that treatment of hyperglycemia with attainment of euglycemia is difficult to achieve in the elderly. Nondrug therapy often fails because of lifelong eating habits, denture problems, fixed income, and physical handicaps. Drug therapy is fraught with the dangers of hypoglycemia and drug interactions. Compliance with therapy often is poor and leads to conflicts between physician and patient that may be detrimental in the treatment of other diseases in which intervention has proven worthwhile. The third obstacle is the lack of data regarding the adverse effects of labeling and noncompliance issues in the face of a positive screening test. Because obesity is a risk factor for NIDDM and hypertension in conjunction with NIDDM leads to atherosclerosis, screening and treatment for these two conditions are warranted whether or not NIDDM is present concurrently. Medicine is in a dynamic state of flux and, undoubtedly, conflicts over the benefits of early treatment and patient compliance will be resolved. Until then, there is no justification for screening for NIDDM in the elderly.     

Pulmonary function in non-insulin-dependent diabetes mellitus.

BACKGROUND: In type I diabetes mellitus, lung function has been investigated in several clinical studies, but there are few data concerning pulmonary function abnormalities in patients with non-insulin-dependent diabetes mellitus (NIDDM). OBJECTIVES: The aim of this study was to assess the presence of pulmonary function abnormalities in patients with NIDDM and to verify the possible associations between diabetic renal microangiopathy, retinopathy and diabetes control. METHOD AND PATIENTS: Thirty patients with NIDDM were collected and divided into two similar groups: subjects with retinopathy and/or diabetic glomerulopathy (group 1, n = 15) and patients without any complications (group 2, n = 15). 17 were males and 13 females, aged from 45 to 81 years. They had had diabetes for 3-23 years and were studied at the Division of Internal Medicine, with an outpatient service for diabetic patients. All patients were non-smokers. The presence of diabetic glomerulopathy was determined by measuring the 24-hour protein excretion rate using the nephelometric method. The presence of retinopathy was determined by using ophthalmoscopy. Glycosylated hemoglobin was measured as an indicator of glycemic control. We performed a global spirometry and measured pulmonary diffusion capacity by the single-breath method corrected by alveolar volume. RESULTS: We found a significant reduction in lung diffusion capacity for carbon monoxide (DL(CO)) in the group of patients with other signs of diabetic microangiopathy (p < 0.005) and a significative correlation between DL(CO )and the grade of albuminuria (r = -0.83, p < 0.001). CONCLUSIONS: Pulmonary function abnormalities, in particular a reduction in diffusion capacity, are common in patients with NIDDM and signs of diabetic microangiopathy. A possible explanation is related to an impaired pulmonary microvasculature and alveolar epithelial basal lamina.     

Predictors of non-insulin-dependent diabetes mellitus]

A random sampling of males and females aged 20 to 69 (1125 males and 1243 females), residing in Moscow, were investigated. The first screening was in 1979, the final one--in 10 years. The program of the first screening included anthropometry, evaluation of the CVS, carbohydrate and fat metabolism, studies on hereditary aggravation with regard to diabetes mellitus (DM); the program of final screening included the state of carbohydrate metabolism. Data processing was done using methods of multidimensional analysis. Independent signs to be used as predictors of noninsulin dependent diabetes mellitus were shown to be the age of 40 and older, a general GTT index of 16, and atherogenicity coefficient values of 3.5 and lower in men, and the presence of dyslipoproteinemia in women.     

Acarbose treatment of non-insulin-dependent diabetes mellitus

Acarbose is a newly developed inhibitor of intestinal alpha-glucosidase, and in the current study its ability to lower plasma glucose levels was studied in 12 patients with non-insulin-dependent diabetes mellitus, poorly controlled on diet plus sulfonylurea drugs. Patients were studied before and three months after the addition of acarbose to their treatment program, and there was a notable fall in postprandial plasma glucose concentrations that approximated 60 mg/dL. When acarbose therapy was discontinued in five patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a notable reduction in Hb A1c and triglyceride concentrations. Finally, considerable individual variation was noted in the response to acarbose, and the results in four patients were quite dramatic, with striking reductions in both fasting and postprandial glucose concentrations. These data suggest that acarbose may be a useful addition in the treatment of patients with non-insulin-dependent diabetes mellitus.     

Complements in non-insulin-dependent diabetes mellitus with complications

A relation of the complement system to the development of complications in non-insulin-dependent diabetes mellitus (NIDDM) was evaluated by measuring some components of the complement system. CH50, C3, C4 and C3bINA were significantly elevated in subjects with NIDDM as compared with healthy non-diabetic controls. However, CH50 and C3 did not differ between diabetics with and without complications. C4 was higher in diabetics with retinopathy as well as with retinopathy and neuropathy than in diabetics without these complications. ACH50, beta 1Hg1 and C3d were similar in subjects with NIDDM and non-diabetics, and not associated with complications of NIDDM. C3d/C3 in NIDDM without complications was lower than in healthy subjects, but did not significantly differ between the types of complications. These results suggest that the high level of complements in NIDDM might be due to enhanced production of complements and the development of diabetic complications would be related to the elevated level of complements.     

Glomerular charge selectivity in non-insulin-dependent diabetes mellitus

To elucidate the stage of the charge selectivity defect in diabetic nephropathy, urinary excretions of IgG1 and IgG4 were measured in patients with non-insulin-dependent diabetes mellitus (NIDDM) and healthy controls. The molecular weights of IgG1 and IgG4 were the same but their isoelectric points were different. Therefore, by measuring both urinary IgG1 and IgG4 excretions, the stage of charge selectivity impairment in the nephropathy of NIDDM may be elucidated. Results were expressed as urinary excretion rate (IgG1 ER, IgG4 ER) and compared between diabetic patients with different urinary excretion rates of albumin (AER). IgG4 ER increased to the stage in which AER was more than 10 μg/min, whereas IgG1 ER did not increase to the stage of AER between 10 and 100 μg/min. This finding suggests that the charge selectivity defect in the kidney of the NIDDM patient is present at the stage when AER is more than 10 μg/min.     

Rapid insulin initiation in non-insulin-dependent diabetes mellitus

Three insulin-initiation regimens were compared in 43 severely hyperglycemic non-insulin-dependent diabetic patients: a "standard" regimen (Lente insulin once daily), a "rapid" regimen (a mixture of regular and Lente insulins twice daily), and a "rapid/intravenous" regimen (the "rapid" regimen preceded by overnight intravenous infusion of regular insulin). The mean serum glucose level fell more rapidly in both groups receiving "rapid" regimens, reaching less than 200 mg/dl in 3.0 days with the "rapid" regimen compared with 5.9 days with the "standard" regimen (p less than 0.005). Duration of hospitalization was similarly reduced (6.4 versus 9.9 days, p less than 0.0001) as was the cost of hospitalization. In contrast to the "rapid" regimens, symptomatic hypoglycemia was common and adequate glycemic control was rare with the "standard" regimen. Thus, rapid initiation of insulin therapy with 0.5 to 0.6 units/kg per day of a mixture of regular and intermediate-acting insulins given twice daily is effective, safe, and reduces the cost of hospitalization in patients with non-insulin-dependent diabetes mellitus who require insulin treatment.     

Prevalence and incidence trends of non-insulin-dependent diabetes mellitus (NIDDM) in the population of the GDR

Trends of prevalence and incidence rates of non-insulin-dependent diabetes mellitus (non-insulin-treated diabetes mellitus) were assessed in the population of the GDR based upon the National Diabetes Register and the Official Statistical Year Book as sources for the calculations. Within the 25-year follow-up period 1960-1984 the prevalence rose from 4.39%; to 31.95%; the incidence rate from 1.04%; to 3.57%. Age-dependence of the specific rates is characterized by their continuous rise above the age of 30 years reaching the peak prevalence of 146.6%; in 75- to 80-year-olds, that of 14.1%, for the incidence in people aged 70 to 75 years. A significant male preponderance was confirmed between the ages of 30 and 50 years, a significant overwhelming of female NIDDM in the age groups 60 to 90 years. Based on demonstrated correlations between the changes of living standard parameters and the epidemiological trend of NIDDM the conclusion is drawn that overnutrition and reduced muscular activity mainly account for the rise of diabetes morbidity in the population of the GDR.