Lipoprotein(a) in android obesity and NIDDM

OBJECTIVE: To assess the level of serum lipoprotein(a) [Lp(a)] in nonobese and obese NIDDM subjects with android body distribution. RESEARCH DESIGN AND METHODS: Serum Lp(a) levels were measured in 30 long-standing NIDDM patients (duration of diabetes 12.5 +/- 3 years, mean +/- SD), with 15 of the patients being obese of android distribution (BMI > 30 kg/m2 and waist-to-hip ratio > 0.8). In addition, there were 15 android obese nondiabetic subjects and 10 healthy subjects serving as the control group. RESULTS: All groups of patients in this study (diabetic, obese, and obese diabetic) showed significantly higher levels of Lp(a) than the healthy control group. Lp(a) concentrations were significantly higher in NIDDM patients with android type of obesity than in nondiabetic androids (24.1 +/- 5.6 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Significantly greater levels of Lp(a) were found in nonobese subjects with diabetes when compared with obese subjects without diabetes (22.3 +/- 4.1 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Furthermore, Lp(a) serum concentrations were not dependent on the degree of glycemic control (controlled NIDDM 23.6 +/- 5.0 vs. uncontrolled NIDDM 21.4 +/- 2.7 mg/dl, NS), but were much greater in subjects with diabetes complicated by vascular disease (complicated 26.3 +/- 5.0 vs. uncomplicated 20.5 +/- 2.7 mg/dl, P < 0.001). No correlation was found between Lp(a) and other lipid parameters in this study. CONCLUSIONS: Lp(a) levels are significantly elevated in both android-obese and nonobese NIDDM patients regardless of the degree of glycemic control. Lp(a) is an independent risk factor showing greater elevations in those subjects complicated with diabetic vascular diseases.     

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis

OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS:The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.     

Exogenous interleukin-3 enhances IL-4 production by splenic CD4+ cells during the early stages of a Trichinella spiralis infection

We determined serum advanced glycation end-products (AGE) levels in patients with NIDDM and evaluated the relationship between these levels and diabetic complications. The subjects consisted of 125 patients (mean age, 59.2 +/- 11.1 years, duration of diabetes 11.6 +/- 8.9 years, mean HbA1c, 6.8 +/- 1.0%) with stable blood sugar control. Sixty-three healthy volunteers (mean age, 58.3 +/- 12.7 years) served as controls. Serum AGE were measured by a newly developed ELISA method. Serum AGE levels were significantly higher in the diabetic group compared with the normal control group (7.2 +/- 14.6 vs. 3.3 +/- 1.0 mU/ml, P < 0.05). Significant correlations were seen between serum AGE and the degree of diabetic nephropathy. Serum AGE levels of diabetic patients with proliferative retinopathy were significantly higher than those of patients without proliferative retinopathy (5.7 +/- 1.8 vs. 3.1 +/- 1.0 mU/ml, P < 0.025) in the patient groups whose serum creatinine levels were between 2.0 and 3.9 mg/dl, although serum creatinine levels of both groups were not significantly different. Serum AGE levels reflected the severity of diabetic complications, including nephropathy and retinopathy.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

Immune response to glycated and oxidized LDL in IDDM patients with and without renal disease

OBJECTIVE: To study autoantibodies to oxidized and glycated LDL in IDDM patients with and without diabetic nephropathy and in nephropathy-related macroangiopathy RESEARCH DESIGN AND METHODS: The study included 101 IDDM patients with a long duration of diabetes and 54 healthy subjects. Patients were divided into two groups according to their median urinary albumin excretion rate (AER); the normoalbuminuric group had AER <20 microg/min and the albuminuric group >200 microg/min. The groups were matched for age and BMI, and the two diabetic groups were matched for duration of diabetes and glycemic control. Antibodies against oxidized LDL (using malondialdehyde-modified LDL as the antigen) and against glycated LDL were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean antibody levels against glycated LDL were higher in IDDM patients (0.305 +/- 0.399) than in healthy subjects (0.166 +/- 0.22 optical density [OD]; P = 0.019), but levels did not differ significantly between normoalbuminuric and albuminuric IDDM patients (0.258 +/- 0.354 vs. 0.388 +/- 0.459, respectively). Among the three groups, antibody levels to oxidized LDL did not differ. IDDM patients showed an inverse correlation between antibodies to oxidized LDL and HbA1 (r = -0.211, P = 0.04). The antibody levels to glycated and oxidized LDL did not differ among albuminuric IDDM patients with or without clinical macroangiopathy. CONCLUSIONS: Antibodies to glycated and oxidized LDL do not seem to associate with diabetic nephropathy or nephropathy-related macroangiopathy.     

Renal and cardiovascular predictors of 9-year total and sudden cardiac mortality in non-insulin-dependent diabetic subjects

BACKGROUND: The objective was to evaluate the impact of urinary albumin excretion rate (UAER), glomerular filtration rate (GFR) and subclinical autonomic neuropathy (SANP) on 9-year total (TM) and sudden cardiac mortality (SCM) in recently diagnosed (< 1 year; RD; n = 150) and known (mean duration 11 years; KD; n = 146) NIDDM subjects. METHODS: The study was prospective and controlled (n = 150). Mortality predictors were analysed by logistic regression analysis. The dependent variables were TM and SCM, the predictors were UAER, GFR, SANP, age, gender, BMI, mean arterial pressure (MAP), fasting serum cholesterol, HDL-cholesterol, triglycerides, insulin, haemoglobin A1c, diabetes duration, QTc-interval (ECG), coronary heart disease (CHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), congestive heart failure (CHF), antihypertensive therapy, and smoking habits. RESULTS: CHD predicted TM and SCM in both RD (P = 0.041 and 0.029) and KD (P = 0.034 and 0.006). PVD predicted TM and SCM in KD only (P = 0.001 and 0.003). CVD predicted TM and SCM in RD only (P = 0.001 and 0.017). In RD male gender (P = 0.049), fasting serum cholesterol (P = 0.007) and CHF (P = 0.001) predicted TM and in kDa haemoglobin A1c (P = 0.004), age (P = 0.001) and MAP (P = 0.014) predicted TM. Serum triglycerides predicted SCM in both RD and kDa (P = 0.001 and 0.003). SANP predicted TM (P = 0.009) and SCM (P = 0.044) in KD only. GFR (inverse value) predicted TM and SCM (P = 0.04 and 0.027) in kDa only. The UAER did not predict mortality in the diabetic subjects. CONCLUSION: SANP and a slightly reduced GFR still in the normal range predicted mortality in KD. Microalbuminuria (30 < UAER < 300 mg/24 h) did not independently predict 9-year mortality in the NIDDM subjects studied.     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7-16) years in 46 patients [median age 11.8 years (range) 3-16.8 years]. The median age of the adult donors was 34.4 (19-54) years in 59 patients [median age 12.1 years (range) 7-17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of 51chromium-EDTA and 125iodine-hippurate 1-48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2-3 months after transplantation the GFR in recipients of pediatric grafts was 62 +/- 20 ml/min per 1.73 m2 compared with 61 +/- 21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486 +/- 239 versus 362 +/- 158 ml/min per 1.73 m2. From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279 +/- 131 ml/min per 1.73 m2 compared with 273 +/- 123 ml/min per 1.73 m2 in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2-3 months after transplant the mean GFR of grafts from pediatric donors increased to 118% +/- 51%, whereas the GFR of adult donor grafts fell to 60% +/- 22% over the same period. After 4-6 months the ERPF in pediatric grafts was 96% +/- 55% compared with 50% +/- 22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient.     

Renal reserve filtration capacity in growth hormone deficient subjects

In normal subjects, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) acutely increase in response to infusion of amino acids and to low doses of dopamine. It is uncertain whether circulatory growth hormone (GH) is a permissive factor for these stimulatory effects. GFR and ERPF (constant infusion technique using 125I-iothalamate and 131I-hippuran, respectively) were measured before and during the infusion of dopamine and amino acids in 8 GH deficient subjects. The clearance study was repeated during concomitant administration of octreotide to investigate whether this somatostatin analogue would modify the amino acid and dopamine-induced renal haemodynamic changes. Dopamine increased baseline GFR from 89 +/- 3 (mean +/- SEM, n = 8) to 102 +/- 4 ml min-1 1.73 m-2 and ERPF from 352 +/- 19 to 476 +/- 26 ml min-1 1.73 m-2, P less than 0.001 for both. During amino acid infusion GFR and ERPF increased to 108 +/- 3 and 415 +/- 23 ml min-1 1.73 m-2, respectively, P less than 0.001 for both. Octreotide did not significantly decrease baseline and dopamine-stimulated renal haemodynamics but lowered the amino acid-stimulated GFR (98 +/- 4 ml min-1 1.73 m-2, P less than 0.05) and ERPF (381 +/- 18 ml min-1 1.73 m-2, P less than 0.05). Basal plasma glucagon concentrations were not suppressed by octreotide, whereas the amino acid-induced increments in plasma glucagon were partially inhibited. It is concluded that GH is not a necessary factor for the stimulatory effects of amino acids and dopamine on renal haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)     

NIDDM in the elderly

OBJECTIVE: We conducted this study to assess the metabolic alterations in elderly patients with NIDDM. RESEARCH DESIGN AND METHODS: Healthy, lean (n = 15; age, 73 +/- 1 years; BMI, 23.8 +/- 0.5 kg/m2), and obese (n = 10; age, 71 +/- 1 years; BMI, 28.9 +/- 1.2 kg/m2) control subjects and lean (n = 10; age, 75 +/- 2 years; BMI, 24.0 +/- 0.5 kg/m2) and obese (n = 23; age, 73 +/- 1 years; BMI, 29.9 +/- 0.7 kg/m2) NIDDM patients underwent a 3-h glucose tolerance test, a 2-h hyperglycemic glucose clamp study, and a 3-h euglycemic glucose clamp study with tritiated glucose methodology to measure glucose production and disposal rates. RESULTS: Waist-to-hip ratio (WHR) was greater in both lean and obese NIDDM patients than in control subjects. Insulin responses during the oral glucose tolerance test were similar in obese subjects (control subjects: 417 +/- 64 pmol/l; NIDDM patients: 392 +/- 47 pmol/l) but were reduced in lean NIDDM patients (control subjects: 374 +/- 34 pmol/l; NIDDM patients: 217 +/- 20 pmol/l, P < 0.01). Lean and obese NIDDM patients had absent first-phase insulin responses during the hyperglycemic clamp. Second-phase insulin responses were reduced in lean (P < 0.01 vs. control subjects by analysis of variance) but not obese NIDDM patients. Hepatic glucose output was not increased in lean or obese NIDDM patients. Steady-state (150-180 min) glucose disposal rates were 16% less in lean NIDDM patients (control subjects: 8.93 +/- 0.37 mg.kg LBM (lean body mass)-1.min-1; NIDDM patients: 7.50 +/- 0.28 mg.kg LBM-1.min-1, P < 0.05) and 37% less in obese NIDDM patients (control subjects: 8.17 +/- 0.38 mg.kg LBM-1.min-1; NIDDM patients: 5.03 +/- 0.36 mg.kg LBM-1.min-1, P < 0.001). CONCLUSIONS: Lean elderly NIDDM patients have a profound impairment in glucose-induced insulin release but mild resistance to insulin-mediated glucose disposal. Obese elderly NIDDM patients have adequate circulating insulin, but marked resistance to insulin-mediated glucose disposal. Hepatic glucose output is not increased in elderly NIDDM patients.     

Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.     

Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor reveals the presence of an intron in the gene

OBJECTIVE: Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients. RESEARCH DESIGN AND METHODS: In 30 outpatients with NIDDM and normo- (n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period. RESULTS: Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 +/- 0.20 to 0.97 +/- 0.16 (means +/- SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 +/- 17.4 ml.min-1 (1.73 m2)-1, which decreased to -3.8 +/- 14.8 ml.min-1.(1.73 m2)-1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations. CONCLUSIONS: GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.     

Decrease in glomerular filtration rate in Japanese patients with type 2 diabetes is linked to atherosclerosis

OBJECTIVE: We assessed the effects of atherosclerosis on the glomerular filtration rate (GFR) in patients with type 2 diabetes and who had micro- or normoalbuminuria. RESEARCH DESIGN AND METHODS: A total of 61 Japanese patients with type 2 diabetes were recruited from inpatients of Osaka City University Hospital. They ranged in age from 40 to 69 years (28 men and 33 women). Each subject collected a 24-h urine sample for quantitative analysis of albumin. Absence of albuminuria was defined as a urinary albumin excretion level of <30 mg/24 h (n = 36) and microalbuminuria as a level of 30-300 mg/24 h. The GFR was estimated using 99mTc diethylenetriamine pentaacetic renogram method. As indexes of atherosclerosis, we measured the intimal-medial thickness (IMT) and distensibility of the carotid artery using high-resolution B-mode ultrasonagraphy and an echo-tracking system. We measured the resistance index (RI) of the renal interlobar arteries by pulsed Doppler sonography. RESULTS: The clinical characteristics of type 2 diabetic patients with and without microalbuminuria did not differ except for duration of diabetes, which was longer in the patients with microalbuminuria. GFR also did not differ between the patients with and without microalbuminuria. GFR was significantly correlated with the patient's age (r = -0.256, P < 0.05), carotid IMT (r = -0.326, P < 0.05), carotid stiffness beta (r = -0.449, P < 0.001), and renal arterial RI (r = -0.365, P < 0.05). In multiple regression analysis, independent factors associated with GFR were carotid IMT (R2 = 0.108, P = 0.0102), carotid stiffness beta (R2 = 0.208, P = 0.0003), and renal artery RI (R2 = 0.130, P = 0.0043). CONCLUSIONS: The decline in GFR in type 2 diabetic patients in the early stages of nephropathy may be due in part to atherosclerosis.     

Stiffness indexes beta of the common carotid and femoral arteries are associated with insulin resistance in NIDDM

OBJECTIVE: To investigate the association between arterial wall stiffness indexes beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin resistance in NIDDM subjects in a cross-sectional study. RESEARCH DESIGN AND METHODS: We evaluated the arterial stiffness indexes beta of CCA and FA using an ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the diabetes center in Osaka City University Hospital, compared with 120 age- and sex-matched control subjects. Insulin sensitivity indexes were evaluated using a euglycemic-hyperinsulinemic clamp. RESULTS: Stiffness indexes beta of both CCA and FA were significantly higher in NIDDM subjects than in control subjects (CCA 18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7 +/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r = -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of diabetes, and mean blood pressure. In stepwise multiple regression analyses, insulin sensitivity index and duration of diabetes were identified as significant independent variables for stiffness indexes beta in both CCA and FA (CCA R2 = 0.249, P = 0.0003; FA R2 = 0.336, P < 0.001). CONCLUSIONS: Arterial stiffness indexes beta of CCA and FA were associated with insulin resistance in NIDDM subjects.     

Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?

The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.     

Structural basis of diabetic nephropathy in microalbuminuric NIDDM patients: a light microscopy study

The objective of the study was to evaluate early structural changes occurring in patients with non-insulin-dependent diabetes mellitus (NIDDM) and microalbuminuria by light microscopy. Basal renal biopsy was performed in patients who were subsequently randomized to different antihypertensive treatments. Fourteen NIDDM patients aged 36-65 years (duration of diabetes 9 +/- 7 years) with microalbuminuria (mean urinary albumin excretion 66 +/- 49 micrograms/min) underwent percutaneous renal biopsy. Control biopsies were obtained from five patients of similar age undergoing nephrectomy for renal neoplasia with normal renal function and no history of renal disease. Control and diabetic biopsies were processed by light microscopy and stained with haematoxylin and eosin, periodic acid Schiff, Masson's trichrome and silver methenamine. The percentage of globally sclerotic glomeruli was evaluated. Glomerular volume was determined using perimeter analysis. A semiquantitative assessment (range 0 to 3+) was made of mesangial sclerosis, interstitial fibrosis, tubular atrophy, arteriosclerosis and arteriolar hyalinosis. Glomerular volume was significantly increased in diabetic as compared to control glomeruli (3.2 +/- 8 vs 1.8 +/- 7, p < 0.01). Mesangial sclerosis (0.9 vs 0, p < 0.0001) and arteriolar hyalinosis (0.91 vs 0.2, p < 0.022) were significantly higher in diabetic compared to control subjects. No significant differences between diabetic and control subjects were found in the percentage of globally sclerotic glomeruli or in the extent of interstitial fibrosis, tubular atrophy and arteriosclerosis. Thus NIDDM patients with microalbuminuria show histological findings consistent with diabetic nephropathy characterized by glomerular hypertrophy, mesangial sclerosis and arteriolar hyalinosis. However, the renal histological changes are mild and appear less marked than in insulin-dependent diabetic patients.     

The central visual field in homonymous hemianopia. Evidence for unilateral foveal representation

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23% +/- 3%, 20% +/- 3% and 15% +/- 3% in Tx, Don, and Nx/Ag and RFR ERPF 35% +/- 4% in Tx, which was significantly higher than 20% +/- 4% and 15% +/- 3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity.     

Alterations in glucose metabolism in the elderly patient with diabetes

OBJECTIVE: To determine the alterations in glucose metabolism in elderly patients with NIDDM. RESEARCH DESIGN AND METHODS: We studied 9 healthy elderly control subjects (73 +/- 1 yr of age; body mass index 25.7 +/- 0.4 kg/m2) and 9 untreated elderly NIDDM patients (72 +/- 2 yr of age; BMI 25.9 +/- 0.5 kg/m2). Each subject underwent a 3-h oral glucose tolerance test (40 g/m2); a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above basal); and a 4-h euglycemic insulin clamp (40 mM.m2.min-1). Tritiated glucose methodology was used to measure glucose production and disposal rates during the euglycemic clamp. RESULTS: Patients with NIDDM had a higher fasting glucose (9.3 +/- 0.3 vs. 5.1 +/- 0.1 mM in control subjects vs. NIDDM patients, respectively, P < 0.001) and a greater area under the curve for glucose during the OGTT (16.0 +/- 0.6 vs. 6.7 +/- 0.3 mM in control subjects vs. NIDDM patients, respectively, P < 0.01) than the healthy control subjects. During the hyperglycemic clamp, patients with NIDDM had an absent first-phase insulin response (112 +/- 6 vs. 250 +/- 31 pM in control subjects vs. NIDDM patients, respectively, P < 0.01), and a blunted second-phase insulin response (159 +/- 11 vs. 337 +/- 46 pM in control subjects vs. NIDDM patients, respectively, P < 0.01). Before the euglycemic clamp, fasting insulin (99 +/- 5 vs. 111 +/- 10 pM in control subjects vs. NIDDM patients, respectively) and hepatic glucose production (11.8 +/- 0.7 vs. 11.5 +/- 0.5 mumol.kg-1-min-1 in control subjects vs. NIDDM patients, respectively) were similar. Steady-state (180-240 min) glucose disposal rates during the euglycemic clamp were slightly, but not significantly, higher in the normal control subjects (36.5 +/- 1.1 vs. 33.1 +/- 1.9 mumol.kg-1-min-1 in control subjects vs. NIDDM patients, respectively, NS). CONCLUSIONS: We conclude that NIDDM in nonobese elderly subjects is characterized by a marked impairment in insulin release. This may be attributable to the toxic effects of chronic hyperglycemia on the beta-cell. When compared with age-matched control subjects, the NIDDM patients showed no increase in fasting insulin or hepatic glucose production, and insulin resistance was mild.     

Urinary albumin excretion rate and glomerular filtration rate in single-kidney type 2 diabetic patients

OBJECTIVE: To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN). RESEARCH DESIGN AND METHODS: Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 +/- 9 years; diabetes duration 8.5 +/- 7 years), 17 SKN (2 men, age 57 +/- 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method. RESULTS: SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 microg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 microg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 +/- 21.4 ml x min(-1) x 1.73 m(-2)) and SKD patients (73.0 +/- 21.5 ml x min(-1) x 1.73 m(-2)) were similar but higher than the one-kidney GFR (GFR / 2) of the age-, sex-, and BMI-matched normal individuals (50.5 +/- 9.0 ml x min(-1) x 1.73 m(-2)) and normoalbuminuric type 2 diabetic patients (54.0 +/- 11.6 ml x min(-1) x 1.73 m(-2)). CONCLUSIONS: Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.     

Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus

BACKGROUND: Several studies had suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. METHODS: We prospectively studied the prevalence of NDRD among a Chinese NIDDM population. Renal biopsy specimens were evaluated with light-, immunohistological and electron-microscopy. The cohort consisted of 51 patients who had NIDDM and proteinuria > 1 g/24 h. RESULTS: Patients with both isolated diabetic nephropathy (DN, n = 34) and NDRD (n = 17) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and glycosylated haemoglobin levels, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had microscopic haematuria (P = 0.043) or non-nephrotic proteinuria (P = 0.004). IgA nephropathy accounted for 59% of the NDRD identified. CONCLUSIONS: In this study, microscopic haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients presenting with renal disease.     

Epidemiological, viral and serological studies concerning the evolution of some acute respiratory diseases between November 1992 and March 1993 in nine districts of the south-east area of Romania

Alterations in core lipid composition of lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM) patients have suggested that the heteroexchange of neutral lipids between HDL and the apo B-containing lipoproteins may be enhanced. For this reason, we studied cholesteryl ester transfer (CET) in ten sulfonylurea-treated patients with stable NIDDM. CET measured in all NIDDM subjects with an assay of mass transfer was significantly greater than that of controls at 1 and 2 h (P < 0.001); the transfer of radiolabeled CE also was increased in a subset of four of the NIDDM group (NIDDM k = 0.21 +/- 0.04 vs. control k = 0.10 +/- 0.05; P < 0.05). A weak correlation was demonstrable between the mass of CE transferred at 1 h and diabetic control expressed as plasma fructosamine (r = 0.58, P < 0.09). To characterize this disturbance in CET further, the donor (HDL + VHDL) and acceptor (VLDL + LDL) lipoprotein fractions were isolated by ultracentrifugation at d 1.063 g/ml from NIDDM and control plasma and a series of recombination experiments were performed. Combining NIDDM acceptor with control donor fractions that contained HDL and CETP and not the combination of NIDDM donor and control acceptor lipoproteins resulted in an accelerated CET response identical to that observed in NIDDM whole plasma. This observation indicated that the abnormality in CET in NIDDM was associated with the VLDL + LDL fraction.(ABSTRACT TRUNCATED AT 250 WORDS)