Preperitoneal fat deposition estimated by ultrasonography in patients with non-insulin-dependent diabetes mellitus

Preperitoneal fat is an indicator of visceral fat deposition, which is closely related to atherosclerosis and coronary heart disease in obese patients. We assessed the relationship of preperitoneal fat deposition and various clinical characteristics in 90 patients with non-insulin-dependent diabetes mellitus (NIDDM). Preperitoneal and subcutaneous fat deposition were measured by ultrasonography. In both the male and female diabetics, preperitoneal fat levels were significantly higher than in age-matched healthy subjects. We also determined blood pressures, fasting plasma glucose, glycosylated hemoglobin A1c, serum lipids, fasting immunoreactive insulin (FIRI), daily urinary C-peptide (CPR), serum leptin, urinary albumin excretion and body mass index (BMI). Of these parameters, BMI, FIRI, leptin and daily urinary CPR were positively correlated with preperitoneal fat deposition. Patients with diet therapy alone showed significantly higher preperitoneal fat levels than those receiving insulin therapy. In female, patients with increased preperitoneal fat showed higher prevalence of hypertension than those with decreased fat. Macroalbuminuric patients had a lower preperitoneal fat than microalbuminuric and normoalbuminuric patients. Patients with proliferative retinopathy exhibited lower preperitoneal fat than did those without retinopathy. Preperitoneal fat levels were positively correlated with motor or sensory nerve conduction velocity. Conclusion: The present findings suggest that in NIDDM patients, increased preperitoneal fat deposition is closely associated with obesity, hypertension and hyperinsulinemia, and negatively modulates diabetic microangiopathy including nephropathy, retinopathy and neuropathy.     

Evidence of impaired gallbladder function in patients with non-insulin-dependent diabetes mellitus by quantitative cholescintigraphy

Non-insulin-dependent diabetes mellitus (NIDDM) is considered to predispose impaired gallbladder function and an increased prevalence of gallbladder disease. The aim of this study was to evaluate the gallbladder function of patients with NIDDM by quantitative technetium-99m-labeled imino-diacetic acid analogue (Tc-99m DISIDA) cholescintigraphy. One hundred and forty-five NIDDM patients (100 males, 45 females; age: 58.7+/-9.5 years) with the absence of autonomic or peripheral neuropathy and without gallbladder or liver disorders were enrolled in this study. The patients were categorized by blood sugar control (HbA(1c)> or =10% as a poor blood sugar control group and HbA(1c)<10% as a good blood sugar control group) and disease duration (diabetic duration > or =10 years as a longer-duration group and diabetic duration <10 years as a shorter-duration group). In addition, 60 normal controls (38 males, 22 females; age: 59.1+/-10.2 years) were also studied for comparison. All NIDDM patients and normal controls underwent Tc-99m DISIDA cholescintigraphy, and the filling fraction (FF) and ejection fraction (EF) of gallbladder were calculated. The results showed significant difference between (1) NIDDM patients versus normal controls in FF and EF, (2) poor versus good blood sugar control of NIDDM patients in FF and EF, and (3) longer versus shorter disease duration of NIDDM patients in FF and EF. Our study, including a large number of subjects, showed that gallbladder function of patients with NIDDM is more impaired than the normal controls; and impaired gallbladder function in NIDDM patients is related to disease duration and blood sugar control.     

Evaluation of gallbladder motility: comparison of two-dimensional and three-dimensional ultrasonography

Since impaired gallbladder emptying contributes to gallstone formation, the evaluation of gallbladder motility requires accurate methodology. Recently developed 3-dimensional ultrasonography may take into account various gallbladder shapes more accurately than conventional 2-dimensional ultrasonography. Therefore, volumes of water-filled balloons of various sizes were determined in vitro by 2-dimensional ultrasonography with the sum of cylinders method and by 3-dimensional ultrasonography. Also, in 15 gallstone patients and 6 healthy volunteers, fasting gallbladder volumes and postprandial motility were determined by both methods. Volumes of water-filled balloons as measured by both methods correlated strongly with true volumes (R= 0.93 for 2-dimensional and R = 0.98 for 3- dimensional ultrasonography). Gallbladder volumes measured by both methods were also correlated (R = 0.66, P <0.001). In gallstone patients, 3-dimensional ultrasonography yielded smaller gallbladder volumes than 2-dimensional ultrasonography (P = 0.007), but not in healthy subjects. With both methods, gallstone patients exhibited decreased postprandial gallbladder motility compared to healthy subjects. In conclusion, gallbladder volume measurements by 3-dimensional and 2-dimensional ultrasonography are strongly correlated.Nevertheless, in gallstone patients, gallbladder volumes by 3-dimensional ultrasonography tend to be smaller than by 2-dimensional ultrasonography, possibly due to interference of gallstones with the volume measurement.     

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus.

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.     

Intracellular metabolism in patients with insulin-dependent and non-insulin-dependent diabetes mellitus

Slow infusion of neutral insulin causes in patients with insulin dependent and noninsulin dependent diabetes mellitus diverse changes in the levels of cAMP, cGMP and the cAMP/cGMP ratio in leukocytes in spite of one-type changes in the concentration of contrainsular hormones in the venous blood: in patients with noninsulin dependent DM a raised cAMP/cGMP factor was lowered whereas in patients with insulin dependent DM it was increased. The authors put forward for discussion the problem of the postreceptor mechanisms of tissue insulin resistance in noninsulin dependent DM and a possibility of the use of the above indices for differential diagnosis of DM types.     

Improvement of esophageal and gastric motility after 2-week treatment of oral erythromycin in patients with non-insulin-dependent diabetes mellitus

Forty-five patients with non-insulin-dependent diabetes mellitus (NIDDM) were enrolled in the study. Before and after the 2-week treatment course of oral erythromycin, esophageal (the mean transit time, MTT) and gastric motility (the halftime of gastric emptying, GETt1/2) were evaluated by radionuclide labeled liquid and solid meals. Meanwhile, the fasting blood sugar (FBS) levels were monitored. After a 2-week erythromycin treatment, MTT shortened from 9.32+/-1.12 to 6.28+/-0.91 s and GETt1/2 shortened from 210.2+/-24.3 to 128.3+/-30.1 min. Meanwhile, FBS decreased from 198.2+/-30.1 to 121.5+/-21.3 mg/dl (P value <.05). We conclude that a 2-week treatment course of oral erythromycin can significantly improve esophageal and gastric motility which results in a better control of blood sugar in patients with NIDDM.     

Limitations of diet therapy in patients with non-insulin-dependent diabetes mellitus

Sixty-one patients with non-insulin-dependent diabetes mellitus and fasting blood glucose of 12.0 +/- 0.6 mmol/l were studied before and after dietary treatment in an outpatient setting. At the start of the study 33 patients were obese (body mass index greater than 27.0 kg/m2). Twenty patients were newly diagnosed, median known duration of diabetes in the others was 5 years. Beta-cell function was measured by the release of C-peptide after i.v. injection of 1 mg glucagon (area under the curve of C-peptide = AUC-cp), as well as calculated according to the formulae of Matthews. Insulin action was estimated by measurement of fasting blood glucose, insulin and free fatty acids (FFA) concentrations. Non-obese patients showed more severe beta-cell deficiency than the obese ones (AUC-cp 2586 +/- 158 vs. 3294 +/- 277 pmol/l per 15 min), and did not improve in metabolic control during treatment. In the obese patients three response patterns to treatment were observed: weight loss and improvement in metabolic control accompanied primarily with increased beta-cell function or increased insulin action, or worsening of metabolic control. Those with less impaired beta-cell function and shorter known duration of diabetes showed the most favourable response. In conclusion: non-obese type 2 diabetes patients with fasting glucose levels above 10 mmol/l do not improve on dietary treatment alone; in obese type 2 diabetics weight reduction is essential and results in metabolic improvement, irrespective of the preceding fasting blood glucose concentrations. Improved beta-cell function as well as increased insulin action are responsible for this improvement.     

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.     

Myocardial infarct size and mortality in patients with non-insulin-dependent diabetes mellitus

Abstract. Objectives. To study the infarct size and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in non-diabetic subjects with their first acute myocardial infarction. Design. Seven year follow-up study of large representative cohorts of patients with non-insulin-dependent diabetes mellitus and non-diabetic subjects (study 1) and the FINMONICA acute myocardial infarction register study in 1988-89 (study 2). Setting. Populations of the districts of the Kuopio University Hospital and Turku University Central Hospital (study 1). Populations of Kuopio and North Karelia provinces and Turku/Loimaa area (study 2). Subjects. Study 1: 1059 patients with non-insulin dependent diabetes mellitus and 1373 non-diabetic subjects aged 45–64 years at baseline; during the follow-up 166 patients with non-insulin-dependent diabetes mellitus (91 men and 75 women) and 30 non-diabetic subjects (25 men and five women) were hospitalized for their first acute myocardial infarction. Study 2: 1622 patients aged 25–64 years hospitalized for their first acute myocardial infarction; 144 patients (90 men and 54 women) had non-insulin-dependent diabetes mellitus and 1153 (890 men and 263 women) were non-diabetic. Main outcome measures. The infarct size was assessed on the basis of maximum levels of serum cardiac enzymes (studies 1 and 2) and QRS-score (study 1). Results. No differences were found in maximum levels of serum cardiac enzymes between diabetic and non-diabetic patients. Similarly QRS-score gave no suggestion of a difference in infarct size between diabetic and non-diabetic patients. In both studies mortality before hospital admission was similar in diabetic and non-diabetic patients, but mortality within 28 days from hospital admission was twice as high in diabetic patients as in non-diabetic patients. Cardiac failure was the main cause of death significantly more often in diabetic patients than in non-diabetic patients (study 2). Conclusions. Poorer prognosis of acute myocardial infarction in diabetic patients appears not to be explained by a larger infarct size but probably by adverse effects of the diabetic state itself on myocardial function.     

Gastrointestinal motility disorders in patients with diabetes mellitus

Abstract. Disturbed gastric and small intestinal motility is an often overlooked clinical problem. Delayed gastric emptying of liquid and/or solid food in patients with type 1 and type 2 diabetes (gastroparesis diabeticorum) occurs in approximately 50% of the patients. Also, the interdigestive gastric and small intestinal motility is often affected. There is only a weak correlation between symptoms and objectively measurable motor disturbances. Patients with severe upper gastrointestinal symptoms usually have disturbed motility, but most patients with impaired motility are asymptomatic. Recent studies have clearly shown that, in addition to autonomic neuropathy, acute metabolic derangements are likely to contribute to disturbed motility. Elevated glucose levels impair gastric and small intestinal motility during fasting and after food intake. Hyperinsulinemia per se has effects similar to hyperglycaemia on the stomach and small bowel, and may be a mediator of the effects of hyperglycaemia in healthy subjects. The impact of insulin on motility in diabetic patients is still unclear. Treatment of the gastric motility disorder should include a stabilization of gastric emptying. Different therapeutic modes may be useful, e.g. application of prokinetic drugs and optimizing the metabolic situation.     

Behaviors predicting foot lesions in patients with non-insulin-dependent diabetes mellitus

Associations between specific foot-care behaviors and foot lesions in patients with non-insulin-dependent diabetes mellitus were prospectively investigated. Data from a randomized controlled trial for preventing diabetic foot lesions were analyzed as a prospective cohort using logistic regression. Independent variables included foot-care behaviors, patient self-foot examination, going barefoot, availability of foot-care assistance, and visits to health-care providers. The dependent variable was a foot wound on each foot at follow-up. In the final multivariate model, patients who rarely lubricated their feet had an increased risk of foot lesions. Increasing patient use of emollients may be key to preventing foot lesions.     

Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus

Objectives. This study sought to determine whether nitric oxide-mediated vasodilation is abnormal in patients with non-insulin-dependent diabetes mellitus.Background. Multiple investigations, both in experimental models and in patients with insulin-dependent diabetes mellitus, demonstrate impaired endothelium-dependent vasodilation. Decreased availability of endothelium-derived nitric oxide may contribute to the high prevalence of vascular disease in diabetes.Methods. Vascular reactivity was measured in the forearm resistance vessels of 21 patients with non-insulin-dependent diabetes mellitus and 23 matched healthy control subjects. No patient had hypertension or hypercholesterolemia. Each subject was protreated with aspirin to inhibit endogenous production of vasoactive prostanoids. Methacholine chloride (0.3 to 10 μg/min) was administered through a brachial artery cannula to assess vasodilation to endothelium-derived nitric oxide. Sodium nitroprusside (0.3 to 10 μg/min) was infused to evaluate vasodilation to an exogenous nitric oxide donor. Verapamil (10 to 300 μg/min) was administered to distinguish impaired nitric oxide-mediated vasodilation from general dysfunction of vascular smooth muscle. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each agent. To assess the role of vasoconstrictor prostanoids, a subset of eight diabetic subjects were reexamined in the absence of aspirin treatment.Results. Basal forearm blood flow in diabetic and nondiabetic subjects was comparable. The forearm blood flow responses to both methacholine chloride and nitroprasside were significantly attenuated in diabetic compared with nondiabetic subjects (p < 0.005 by analysis of variance for both agents). In contrast, the response to verapamil was not significantly different between the groups (p > 0.50). The forearm blood flow responses to these agents were not significantly affected by cyclooxygenase inhibition.Conclusion. Nitric oxide-mediated vasodilation is impaired in non-insulin-dependent diabetes mellitus. Vasoconstrictor prostanoids do not contribute significantly to vascular dysfunction. The attenuated response to exogenous as well as endogenous nitric oxide donors suggests that the abnormality is due to increased inactivation of nitric oxide or to decreased reactivity of the vascular smooth muscle to nitric oxide.     

Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Proteins and lipids are among the prime targets for oxidative stress. In the present study, the oxidative stress was evaluated in 55 diabetic patients and 40 healthy subjects by measuring the levels of protein oxidation, lipid peroxidation and some enzymatic and nonenzymatic antioxidants. The oxidative products of protein (PCG) and lipid peroxidation (MDA) and nitric oxide levels in plasma of NIDDM patients were significantly increased. However, the levels of enzymatic (GPx, SOD, catalase in RBC) and nonenzymatic (β-carotene, retinol, vitamin C & E and uric acid) antioxidants of RBC showed a significant decrease in NIDDM patients compared to normal subjects. Serum protein analysis by polyacrylamide gel electrophoresis (PAGE) showed the significant difference in the ceruloplasmin, transferrin, albumin, retinal binding protein, etc. in diabetic patients compared to healthy controls. In conclusion, the results suggest that increased protein oxidation, lipid peroxidation and NO levels, decreases the levels of enzymatic and nonenzymatic antioxidants and playing a major role in diabetic complications.     

Urinary orosomucoid excretion rate in patients with non-insulin-dependent diabetes mellitus

Urinary excretion rate and clearance of alpha 1-acid glycoprotein (orosomucoid), a major serum glycoprotein which is more anionic (pI 2.7) than albumin (pI 4.7) were measured by RIA in timed overnight urine samples from non-insulin-dependent diabetic patients with different urinary albumin excretion rate and from healthy controls. The 50th percentiles of urinary orosomucoid excretion rate in patients with normo-, micro-, and macroalbuminuria were larger than those in healthy controls. Urinary excretion rate and clearance of orosomucoid increased in parallel with increase in albumin excretion rate in diabetic patients with an albumin excretion rate of more than 10 micrograms/min. On the basis of their levels of urinary orosomucoid excretion, patients with normoalbuminuria of less than 10 micrograms/min could be divided into two groups, one with a normal and the other with an elevated urinary orosomucoid excretion rate. The findings suggest that kidneys of diabetic patients with an albumin excretion rate of more than 10 micrograms/min are unable to distinguish the difference in pI between albumin and orosomucoid, and that a subgroup with an elevated orosomucoid excretion rate may be present among diabetics with normoalbuminuria.     

Detection of liver membrane antibodies in patients with non-insulin-dependent diabetes mellitus

Circulating liver membrane antibodies (LMAb) were examined in 71 patients with non-insulin-dependent diabetes mellitus (NIDDM) without liver dysfunction and 16 cases of KK mouse as a model of obese diabetic animals. LMAb were detected in 10 NIDDM patients (14.1%). Fasting blood glucose, glycosylated serum albumin (G-Alb), and glycosylated hemoglobin A1 (HbA1) levels were compared with LMAb-positive and negative groups. The G-Alb levels and HbA1 levels of the LMAb-positive group were significantly higher (p less than 0.05 and p less than 0.01, respectively) than those of the LMAb-negative group. In addition, there were no differences in histological findings in KK mouse liver between the LMAb-positive and negative cases. These results revealed that the state of continued high blood glucose directly or indirectly influence the autoimmunity and clinical features of NIDDM patients.     

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.     

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.