Prospective follow-up study of renal function in type 2 diabetes

Type 2 diabetes mellitus is the main cause of increase in patients suffering from end-stage renal failure in France. We performed an observational study of the change in renal function of type 2 diabetic patients, attending our diabetology clinic. Clinical and biological data were regularly entered in an informatic database (Pénélope, Poitiers University Hospital). We prospectively followed 351 type 2 diabetic patients (age at diagnosis: 40 to 75 years), for 32 months (extremes: 1-120). Renal function was graded in 4 stages according to plasma creatinine and urinary albumin excretion (UAE) determined by nephelometry on random urinary sample: absent (UAE < 20 mg/L et creatinine < 150 mumol/L), incipiens (UAE 20 to 200 mg/L and creatinine < 150 mumol/L), established (UAE = 200 mg/L et creatinine < 150 mumol/L) advanced (creatinine = 150 mumol/L). Glycated haemoglobin (HbA1c) was determined by HPLC. Systolic/Diastolic Blood Pressure (SBP/DBP) was measured with a mercury sphygmomanometer. We defined renal events as the change from one stage of nephropathy to a higher one. A total of 351 type 2 diabetic subjects were studied: 194 men/157 women mean age 63 +/- 11 years, mean diabetes duration 10 +/- 9 yr. At baseline, 206 patients had no nephropathy, 98 incipient nephropathy, 28 established nephropathy and 19-advanced nephropathy. Baseline stage of nephropathy was related to SBP (p < 0.0001), DBP (p = 0.0002), diabetes duration (p = 0.0064) but not HbA1c (p = 0.2182) or sex (p = 0.4794). Among those 332 subjects without baseline advanced nephropathy, 134 progressed in nephropathy. Progression of nephropathy was not related to the presence of hypertension (SBP/DBP > or = 160/95 mmHg) (log-rank = 0.22; p = 0.6377). Conversely, patients with a poor glycaemic control (HbA1c > or = 10%) had a worse renal-event free survival (log-rank = 4.89; p = 0.0269). Glycaemic control is a risk factor for the progression in nephropathy of type 2 diabetic patients.     

Plasma homocysteine and microvascular complications in type 1 diabetes

BACKGROUND: Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally. AIMS: 1) To evaluate the association between fasting plasma homocysteine, type 1 diabetes and its microvascular complications; 2) to elucidate the basis of this association by investigating the major determinants of plasma homocysteine in relation to diabetic microangiopathy. METHODS: We studied sixty-six consecutive patients with type 1 diabetes mellitus of > 10 years duration and normal serum creatinine (< 115 mumol/L, 1.3 mg/dL), and free from clinically detectable cardiovascular diseases. Forty-four non-diabetic controls were also studied. Plasma concentrations of homocysteine, folate and vitamin B12 were investigated together with the C677T mutation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal diabetic complications were evaluated as albumin/creatinine ratio on early-morning, urine spot collection and fundus photographs. FINDINGS: Fasting plasma homocysteine levels were very similar in patients and controls. Patients with microalbuminuria or proliferative retinopathy had significantly higher values than those without: 9.4 +/- 3.1 vs 7.4 +/- 2.8 mumol/L, p < 0.02 and 9.5 +/- 2.6 vs 7.3 +/- 3.0 mumol/L, p < 0.05. This difference was not attributable to confounders, such as age, sex and smoking, nor to dissimilar plasma folate and vitamin B12 concentrations. In contrast, homozygosity for the C677T mutation in the MTHFR gene--the commonest genetic defect linked to moderately increased plasma homocysteine--was significantly more frequent in patients with microalbuminuria and/or proliferative retinopathy (50% vs 13%, p < 0.004), odds ratio 6.7 (95% CI 1.7-27.6). CONCLUSIONS: Type 1 diabetes as such is not associated with increased plasma homocysteine levels, though patients with microalbuminuria and/or proliferative retinopathy display significantly higher values than those without. This difference is not attributable to obvious confounders, nor to differences in vitamin status, and may be partly mediated by genetic factors. Plasma homocysteine, together with other diabetes-related noxae, may thus be in a position to contribute to the development of nephropathy and the progression of retinopathy.     

Postprandial hypertriglyceridemia and carotid intima-media thickness in north Indian type 2 diabetic subjects

Hypertriglyceridemia is an important risk factor for coronary heart disease (CHD) and in the development of atherosclerosis, especially in subgroups of the population like those with type 2 diabetes. Although triglycerides are generally increased in the postprandial period, the association between postprandial triglyceride (ppTG) levels and atherosclerosis has not been investigated in north Indian type 2 diabetic subjects known to have a very high prevalence rate of premature CHD and insulin resistance. To investigate the role of ppTG levels in atherosclerosis in type 2 diabetes, we examined the correlation between ppTG levels and carotid intima-media thickness (IMT). Carotid IMT was determined by high resolution B-mode ultrasonography in 86 newly detected type 2 diabetic subjects (1-12 months duration) having good glycemic control (HbA(1C)<7%) and 45 non-diabetic subjects matched according to age and body mass index (BMI). Plasma glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were measured after overnight fasting. Plasma insulin and glucose were also measured 2h and plasma triglycerides 4h after breakfast. The mean carotid IMT in diabetic subjects was higher than those in non-diabetic subjects (0.77+/-0.15 mm versus 0.53+/-0.16 mm, P<0.001). Based on the fasting and postprandial triglyceride levels, the diabetic subjects were divided into three groups: normo-normo (NN); normo-hyper (NH); hyper-hyper (HH) [NN: fTG<1.70 mmol/L and ppTG<2.30 mmol/L; NH: fTG<1.70 mmol/L and ppTG>2.30 mmol/L; HH: fTG>1.70 mmol/L and ppTG>2.30 mmol/L]. Carotid IMT was significantly increased in the NH (0.79+/-0.09 mm) and HH (0.82+/-0.06 mm) groups compared with the NN group (0.59+/-0.09 mm, P<0.001). Although ppTG, age, fasting LDL-cholesterol, HOMA-estimated insulin resistance, HbA(1C) were all independently correlated with carotid IMT, age and ppTG levels had the strongest statistical influence (P<0.002).     

Glycaemic control and obesity are the major determinants of diabetic dyslipidaemia in Hong Kong Chinese

OBJECTIVES: Dyslipidaemia plays a major role in the increased mortality in diabetes. Our aim was to address the quantitative abnormalities and determinants for lipid abnormalities in Chinese Type 2 diabetic patients. MATERIAL AND METHODS: In this study, we examined 1 279 Chinese type 2 diabetic patients and compared them with 959 non-diabetic control subjects. RESULTS: Of the 1 279 Type 2 diabetic patients, 588 (46.0%) were men and 691 (54.0%) were women. The mean age was 40.4 +/- 8.1 years (median: 41.0 years, range: 16-72 years). Compared to the 959 age- and sex-matched non-diabetic controls, diabetic patients were more obese, had higher blood pressure and adverse lipid profile characterized by high triglycerides and low high-density lipoprotein cholesterol. After adjusting for age, sex, smoking, obesity, use of lipid-lowering drugs and anti-diabetic agents, diabetic patients had higher risk of having hypertriglyceridaemia (>=2.3 mmol/L) and low high-density lipoprotein cholesterol (<0.9 mmol/L) than non-diabetic subjects. The corresponding odds ratios were 2.9 and 1.5, respectively. With multiple regression analysis (stepwise), dyslipidaemia was mainly associated with glycaemia, obesity and age in diabetic patients, and obesity, male gender and age in non-diabetic subjects. CONCLUSION: We have confirmed the high prevalence and increased risk of dyslipidaemia in Chinese type 2 diabetic patients. The long-term significance of these lipid abnormalities and their synergism on clinical outcomes requires further evaluation.     

Association of serum levels of IGF-I and IGFBP-1 with renal function in patients with type 2 diabetes mellitus.

OBJECTIVE: Our aim was to determine whether serum Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor binding protein-1 (IGFBP-1) levels were different between type 2 diabetic patients and non-diabetic control group. We also aimed to establish any relationship that might exist between the serum IGF-I and IGFBP-1 levels with the urinary albumin excretion (UAE), creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion (as a marker of renal tubular dysfunction) and other parameters (such as age, duration of diabetes, treatment, etc.) in patients with type 2 diabetes mellitus (DM). DESIGN: Fifty-nine type 2 diabetic patients and thirty-one non-diabetic controls were included in this study. RESULTS: Mean serum IGF-I levels in diabetic patients were lower than the non-diabetic controls (158+/-12 vs. 287+/-26microg/l), (p<0.001). Serum IGFBP-1 levels were also higher in type 2 diabetic patients compared to the control group (67+/-5 vs. 35+/-4microg/l), (p<0.001). No relationship was obtained between IGF-I and IGFBP-1 levels with neither UAE nor urinary NAG excretion. A significant negative relationship was observed between creatinine clearance and serum IGFBP-1 level (r=-0.39, p=0.004). In multiple regression analysis IGF-I was independently and negatively associated with age and insulin treatment. On the other hand, IGFBP-1 was negatively related with creatinine clearance and positively related with the duration of diabetes. CONCLUSION: These results suggest that type 2 DM leads to a decrease in the IGF-I while elevating the IGFBP-1 levels. Further studies are needed to clarify a potential role of increased levels of IGFBP-1 in decreased creatinine clearance in type 2 DM.     

Blood levels of total homocysteine in patients with type 1 diabetes (with no complications,diabetic nephropathy and/or retinopathy) and in their non-diabetic relatives

BACKGROUND AND AIM: It has been reported that plasma homocysteine (Hcy) levels in type 1 diabetes (T1DM) patients without renal involvement are higher, similar to or lower than those in healthy controls. METHODS AND RESULTS: We measured plasma Hcy in 60 controls, 79 type 1 diabetics (23 with retinopathy, 22 with nephropathy) and 73 non-diabetic relatives of 30 probands. The female controls had lower levels than their male counterparts: geometric mean 10.5 vs 13.6 mumol/L, p < 0.001. Among the controls, smokers (n = 20) and ex-smokers (n = 12) had higher Hcy levels than non-smokers (n = 28): 13.2 and 13.2 vs 10.9 mumol/L, p < 0.01. Among the diabetics, high plasma Hcy levels were associated with male gender: 11.9 vs 9.1 mumol/L in women, p < 0.01. The patients without complications had higher plasma glucose and hemoglobin A1c (HbA1c) levels (p < 0.001), and lower plasma Hcy (9.2 mumol/L vs 12.2, p < 0.01) and uric acid levels (p < 0.05) than the controls. The patients with nephropathy and higher levels of Hcy (13.0 mumol/L vs 9.0, p < 0.05), and different levels of creatinine (p < 0.01), uric acid (p < 0.01), fibrinogen (p < 0.05), and urinary albumin (p < 0.001) than those with retinopathy. There was no difference in Hcy levels between the patients' relatives and the controls: 11.9 mumol/L in siblings vs 11.6 mumol/L, 13.5 mumol/L in parents vs 12.1 mumol/L. In the control group, plasma Hcy levels were associated with age, gender and smoking; among the diabetics, they correlated with age, gender, smoking, and plasma creatinine and lipoprotein (a) levels. CONCLUSIONS: 1) male gender and smoking are associated with high Hcy levels in healthy people; 2) plasma Hcy levels are lower in T1DM patients than in healthy people (glomerular hyperfiltration and accelerated hepatic transsulfuration?); 3) high Hcy levels are associated with diabetic nephropathy and plasma creatinine levels; and 4) non-diabetic first-degree relatives of type 1 diabetics have normal plasma Hcy concentrations.     

Co-occurrence of hypercalciuria and hypouricaemia in type 2 diabetic patients

The relationship between the urinary excretion of calcium (Ca2+) and uric acid was investigated in 151 Type 2 diabetic patients and 48 normal subjects. In the diabetic patients, uric acid clearance/creatinine clearance (Clurate/Clcr) was higher and the serum level of uric acid was lower than in the normal subjects (Clurate/Clcr: 10.9 +/- 5.8 vs 8.1 +/- 2.6%, p less than 0.001; serum uric acid: 3.4 +/- 86 vs 357 +/- 89 mumol l-1, p less than 0.001). Calcium clearance/Clcr (Clca/Clcr) also increased in the diabetic patients, as did urinary excretion rate, but the serum Ca2+ level was not different to normal control subjects (Clca/Clcr: 2.29 +/- 1.59 vs 1.56 +/- 0.98%, p less than 0.001; Ca2+ excretion rate: 2.24 +/- 1.67 vs 1.63 +/- 1.11 mmol day-1, p less than 0.01; serum Ca2+ level: 2.34 +/- 0.11 vs 2.33 +/- 0.08 mmol l-1). In the diabetic patients, Clcr positively and the serum uric acid negatively correlated with the urinary excretion of Ca2+ (p less than 0.001 for both correlations in the multivariate regression analysis). These data suggest that the diabetic patients have increased fractional excretion of both Ca2+ and uric acid.     

Effect of improving glycemic control on low-density lipoprotein particle size in type 2 diabetes

The current study sought to assess the effect of improving glycemic control in type 2 diabetes on the components of diabetic dyslipidemia, especially low-density lipoprotein (LDL) size. A total of 33 type 2 diabetic patients (48.5% women, age 59.6 +/- 11.1 years, body mass index [BMI] 28.9 +/- 4.9, diabetes duration 6 [0 to 40] years, 40.7% on insulin) were seen at the hospital because of poor glycemic control (hemoglobin A(1c) [HbA(1c)] 10.33% +/- 1.89%). Triglyceride, LDL-cholesterol (LDLc, Friedewald/ ultracentrifugation), high-density lipoprotein HDL-cholesterol (HDLc, direct method), apolipoproteins AI (apoAI) and B (apoB) (immunoturbidimetry), and LDL size (gradient gel electrophoresis) were measured at baseline and after improvement in glycemic control (decrease >/= 1 percentage point in HbA(1c) and final HbA(1c) 相似文献   

Quantitation of forearm glucose and free fatty acid (FFA) disposal in normal subjects and type II diabetic patients: evidence against an essential role for FFA in the pathogenesis of insulin resistance

This study was designed to quantitate glucose and FFA disposal by muscle tissue in patients with type II diabetes and to investigate the relationship between FFA metabolism and insulin resistance. The forearm perfusion technique was used in six normal subjects and two groups of normal weight diabetic patients, i.e. untreated (n = 8) and insulin-treated (n = 6). The latter received 2 weeks of intensive insulin therapy before the study. Plasma insulin levels were raised acutely [950-1110 pmol/L) (130-150 microU/mL)], while the blood glucose concentration was clamped at its basal value [4.9 +/- 0.1 (+/- SE) mmol/L in the normal subjects, 5.7 +/- 0.5 in the insulin-treated diabetic patients, and 5.5 +/- 0.3 in the untreated diabetic patients] by a variable glucose infusion. During the control period, arterial FFA concentrations were similar in the three groups, and they decreased to a comparable extent (less than 0.1 mmol/L) in response to insulin infusion. During the control period, the mean forearm FFA uptake was 2.5 +/- 0.5 mumol/L.min in the normal subjects, 2.9 +/- 0.5 in the insulin-treated patients, and 2.1 +/- 0.5 in the untreated diabetic patients. During the insulin infusion, FFA uptake was profoundly suppressed to similar levels in the normal subjects (0.9 +/- 0.1 mumol/L.min), the insulin-treated diabetic patients (1.1 +/- 0.3), and the untreated diabetic patients (0.9 +/- 0.1; P less than 0.001). Forearm glucose uptake was similar in the three groups during the control period. It increased during the insulin infusion, but the response in both diabetic groups was less than that in the normal subjects. The total amounts of glucose taken up by the forearm during the study period were 5.2 +/- 0.7, 2.6 +/- 0.5, and 2.1 +/- 0.6 mmol/L.min in the normal subjects, the insulin-treated diabetic patients, and the untreated diabetic patients, respectively (P less than 0.01). We conclude that 1) insulin-mediated glucose uptake by forearm skeletal muscle is markedly impaired in type II diabetes and improves only marginally after 2 weeks of intensive insulin therapy; 2) in contrast, no appreciable abnormality in forearm FFA metabolism is demonstrable in insulin-treated type II diabetic patients; and 3) FFA do not contribute to the insulin-treated skeletal muscle insulin resistance that occurs in patients with type II diabetes mellitus.     

Glucose turnover and recycling in diabetes secondary to total pancreatectomy: effect of glucagon infusion

This study was designed to evaluate whether chronic deficiency of pancreatic glucagon in patients with diabetes secondary to total pancreatectomy (PX) is responsible for the commonly observed increase in blood concentrations of gluconeogenic precursors (alanine, lactate, and pyruvate). Seven PX patients were studied on two different occasions: 1) after an overnight insulin infusion (0.15 mU/kg.min) and 2) after an overnight insulin/glucagon infusion (2 ng/kg.min). Five type 1 diabetic individuals were also studied after a similar overnight insulin infusion. In the morning of each study day, [6-3H]glucose and [1-14C]glucose were rapidly injected for determination of total glucose turnover rate [( 6-3H]glucose) and glucose recycling (difference between [6-3H]glucose and [1-14C]glucose turnover rate). Basal concentrations of hormones, glucose, and intermediary metabolites were measured. After overnight insulin infusion, plasma glucose concentration (3.8 +/- 0.4 vs. 6.8 +/- 1.4 mmol/L), turnover rate (8.4 +/- 1.0 vs. 13.7 +/- 1.9 mumol/kg.min), and percent glucose recycling (5.6 +/- 3.9% vs. 19.0 +/- 3.8%) were significantly lower in PX patients than in type 1 diabetic individuals (P less than 0.05-0.01). On the contrary, blood alanine (459 +/- 93 vs. 263 +/- 28 mumol/L), lactate (1157 +/- 109 vs. 818 +/- 116 mumol/L), and pyruvate (71 +/- 8 vs. 42 +/- 3 mumol/L) were significantly higher than those values in type 1 diabetic patients (P less than 0.05-0.01). Insulin/glucagon infusion increased plasma glucose concentration (8.7 +/- 1.5 mmol/L), total turnover (18.1 +/- 1.7 mumol/kg.min), and percent recycling (20.4 +/- 6.6%) to values similar to those in type 1 diabetic subjects. The change in glucose metabolism was associated with a significant drop in blood concentrations of alanine (179 +/- 24 mumol/L), lactate (611 +/- 25 mumol/L), and pyruvate (30 +/- 3 mumol/L; all P less than 0.05-0.01 vs. insulin infusion alone). In PX patients, the glucose turnover rate was inversely correlated with blood concentrations of both alanine (r = 0.67) and lactate (r = 0.71; P less than 0.01). In conclusion, chronic deficiency of pancreatic glucagon in PX patients 1) is associated with a decreased rate of glucose turnover, 2) causes a marked impairment in glucose recycling (an index of the activity of hepatic gluconeogenesis), and 3) increases blood concentrations of alanine, lactate, and pyruvate. All abnormalities are reversed by glucagon.     

Glucose and gluconeogenic substrate exchange by the forearm skeletal muscle in hyperglycemic and insulin-treated type II diabetic patients

To determine the contribution of skeletal muscle to fasting hyperglycemia in noninsulin dependent type II diabetes (NIDDM), the forearm balance of glucose, lactate, and alanine was quantified in 25 control subjects, 21 hyperglycemic (blood glucose: 11.6 mmol/L), and 19 insulin-treated patients with NIDDM (blood glucose: 5.8 mmol/L). Forearm glucose uptake was similar in controls (4.6 +/- 0.6 mumol L-1 min-1) and in hyperglycemic diabetic patients (4.5 +/- 0.9 mumol L-1 min-1). In spite of this, in the diabetic patients lactate (5.1 +/- 0.8 mumol L-1 min-1) and alanine (2.6 +/- 0.4) release by the forearm was 3- and 2-fold higher than in the control group (lactate: 1.7 +/- 0.8, P less than 0.005; and alanine: 1.3 +/- 0.2, P less than 0.05, respectively). The ratio of lactate release to glucose uptake was 57% and 18% in diabetic and control subjects, respectively. Insulin administration did not affect either glucose uptake or the release of gluconeogenic substrates by the forearm. It is concluded that: 1) in fasting patients with NIDDM, glucose is taken up by the skeletal muscle in normal amounts but preferentially used nonoxidatively with lactate formation. This suggests that, although the muscle does not contribute directly to fasting hyperglycemia, it may play an indirect role through an increased delivery of glucose precursors; and 2) insulin-induced normoglycemia is maintained by mechanisms that do not involve the exchange of glucose and gluconeogenic substrates by the skeletal muscle.     

Renal histological lesions in patients with type II diabetes mellitus

Diabetic glomerulosclerosis is the most frequent cause of renal disease in patients with type II diabetes mellitus (DM), sometimes accompanied by vascular lesions. However, other glomerular pathologies are important in these patients. The aim of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) in selected patients with type II DM, and to identify clinical markers that may predict its presence in this population. We reviewed 20 renal biopsies performed on twenty patients with type II DM. Nine of them showed diabetic nephropathy (DN) (45%), whereas eleven showed NDN (55%): 1 IgA nephropathy, 3 vasculitis and 7 membranous nephropathy. We found no differences between the two groups with regard to sex, duration of DM, insulin therapy, glycosylated haemoglobin, proteinuria, presence of nephrotic syndrome, hypertension, serum IgA level or renal size. The NDN group had haematuria in 63.6%, whereas the patients with NDN had it in 44.4% (NS). Body mass index was higher in NDN patients (30 +/- 6.7 vs 22 +/- 2.9; p < 0.01), The same was true for creatinine clearance (82.2 +/- 51.4 ml/m vs 40.4 +/- 19.6 ml/m; p < 0.05). The age at the moment of diagnosis was higher in ND patients (67 +/- 11.2 vs 54.3 +/- 4.6; p < 0.05). The 3 patients who had diabetic retinopathy were found to have DN on renal biopsy (diagnostic specificity = 100%), although 66.7% of the patients with diabetic glomerulopathy had no retinopathy. We conclude that patients with type II DM with renal findings suggesting non-diabetic renal disease frequently it have NDN, and a renal biopsy must be performed. The presence of retinopathy has a predictive value of 100% in predicting DN, therefore its existence may make this diagnostic procedure unneccesary.     

No association between retinopathy and insulin resistance in type 1 diabetes

Intact endothelial cell function has been suggested to be important for insulin action. An association between retinopathy and insulin resistance has been found in type 2 diabetes. To evaluate, whether insulin resistance is related to retinopathy in insulin dependent diabetes, we examined 36 type 1 diabetic patients with various degrees of retinopathy: 7 patients had proliferative, 15 had background and 14 patients had no retinopathy. The three groups were matched for age, sex, body weight and insulin dose. Compared with patients with no retinopathy, those with proliferative retinopathy had a longer (P less than 0.05) duration of diabetes (13 +/- 3 vs 22 +/- 3 years for no vs proliferative retinopathy), and higher (P less than 0.05) serum creatinine (74 +/- 4 vs 97 +/- 8 mumol/l), triglyceride (0.69 +/- 0.04 vs 1.02 +/- 0.17 mmol/l) and diastolic blood pressure (77 +/- 3 vs 90 +/- 10 mmHg) levels. The rate of insulin-mediated glucose metabolism (1 mU euglycaemic insulin clamp) was virtually identical in each diabetic group (4.80 +/- 0.42, 4.90 +/- 0.36 and 4.98 +/- 0.74 mg/kg/min) and 40% below that in 8 matched normal subjects (7.53 +/- 0.53 mg/kg/min, P less than 0.001). In conclusion, proliferative retinopathy is related to long duration of diabetes, incipient nephropathy and hypertension. Insulin resistance characterizes the majority of patients with type 1 diabetes but is unrelated to retinopathy.     

Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.     

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

OBJECTIVE: To determine the relation between plasma leptin concentrations and metabolic control in human diabetes mellitus. DESIGN AND SUBJECTS: Cross sectional study consisting of 156 patients with diabetes mellitus type 1 (n=42), type 2 (n=114), and non-diabetic subjects (n=74). RESULTS: Plasma leptin concentrations were lower (P<0.05) in type 1 (8.3+/-1.7 ng/ml) and type 2 diabetic (14.9+/-1.8 ng/ml) than in non-diabetic humans (18.3+/-1.9 ng/ml). Only female type 1 and type 2 diabetic subjects also had decreased leptin/BMI ratios (P<0.05 vs non-diabetic females). The log rank test identified age-adjusted correlation of plasma leptin concentration with sex (P<0.0004) and body mass index (P<0.0218), but not with glycosylated haemoglobin A1c (P>0.5) in all groups. Plasma leptin was correlated with age (P<0.0058) and serum triglycerides (P<0.0199) in type 1 diabetic patients, and with serum cholesterol (P<0.0059) and LDL (P<0.0013) in type 2 diabetic patients. CONCLUSIONS: Defective leptin production and/or secretion might be present independently of metabolic control in female patients with type 1 or type 2 diabetes mellitus.     

Significant bacteriuria in outpatient diabetic and non-diabetic persons.

AIMS: The prevalence of significant bacteriuria (SB) in diabetes mellitus has not been clearly established. Having previously investigated SB frequency in inpatient diabetic women, we now screened for SB (both asymptomatic and symptomatic forms) in outpatients. METHODS: We examined 511 consecutive outpatients with Type 1 (T1D) or Type 2 diabetes (T2D), and 98 non-diabetic subjects. At least one uncontaminated midstream urine sample was available from 602 subjects: 64 T1D (37 female, age 49 +/- 13 years, diabetes duration 23 +/- 15 years), 441 T2D (212 female, 66 +/- 10 years, 12 +/- 10 years), and 97 healthy control subjects (39 female, 57 +/- 12 years). On the same day, we determined: blood cell count, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), plasma creatinine, urinary creatinine, and urinary albumin excretion (UAE; microg/mg urinary creatinine). RESULTS: The rate of SB was 14.1% in T1D, 9.3% in T2D and 6.2% in control subjects (P = NS). The 50 diabetic patients with SB differed from the 455 diabetic patients without SB in gender (43 male vs. 206 female, P < 0.001), FPG (10.2 +/- 3.6 vs. 9.2 +/- 2.9 mmol/l, P < 0.05), HbA(1c) (7.8 +/- 1.1 vs. 7.5 +/- 1.3%, P < 0.05), and UAE (median 15.6 vs. 7.6 microg/mg, P < 0.01). Eleven diabetic patients with SB had symptoms (vs. 48 without SB, P < 0.05); UAE levels were higher in the 39 asymptomatic diabetic patients with SB than in the 11 symptomatic patients. CONCLUSIONS: The prevalence of SB is similar in outpatient diabetic individuals and in non-diabetic subjects. The main risk factors for SB in diabetic patients were female gender and UAE. The likelihood of asymptomatic SB increased with UAE levels, i.e. with the presence of established microangiopathy. Poor glycaemic control is associated with bacteriuria, either as a cause or consequence of bacteriuria.     

Low fecal elastase-1 in type I diabetes mellitus

BACKGROUND: Previous studies suggested impaired pancreatic exocrine function in type I diabetes patients, but have been limited by small or highly selected samples. Fecal elastase-1 has facilitated evaluation of pancreatic dysfunction in population-based studies. METHODS: 112 type I diabetic patients (age +/- SD: 37 +/- 11 years; 47 % males; diabetes duration: 12.5 +/- 10.5 years) were consecutively selected from main regional diabetes centers in Essen, West-Germany. 116 non-diabetic control subjects, similar with respect to age and sex, were recruited from the same geographical region. Elastase-1 measurement was performed centrally by ELISA (ScheboTech, Germany). RESULTS: Elastase-1 concentrations in type I diabetic patients were significantly lower than in control subjects (median; inter-quartile range: diabetic patients: 227, 98-386 microgram/g stool; non-diabetic subjects: 544, 377-702 microgram/g stool) (p < 0.01). Elastase-1 < 100 microgram/g stool (E1 < 100) was found in 25.9 % of diabetic and 5.2 % of non-diabetic subjects, yielding an age-sex-adjusted prevalence Odds ratio (POR; 95 % CI) for diabetes and E1 < 100 of 6.9 (2.8-19.6). After adjusting for potential confounders (history of gastrointestinal diseases, smoking, alcohol consumption) the strong association remained (POR: 6.7; 2.7-19.2). Among patients with diabetes, E1 < 100 was associated with quality of glycemic control (HbA1c, change per 1 %: POR 1.5; 1.1-2.0), diabetes duration (per year: POR 1.1; 1.03-1.2), and age at diabetes onset (per age year: POR 1.1; 1.02-1.1). No association was found with history of gastrointestinal diseases, smoking, or alcohol consumption (current, life-time). CONCLUSIONS: Fecal elastase-1 concentrations were lower in type I diabetes patients compared to control subjects, indicating impaired pancreatic exocrine function. Low elastase-1 was associated with poor metabolic control and longer diabetes duration.     

The relationship of hyperinsulinaemia to the development of hypertension in type 2 diabetic patients and in non-diabetic subjects

We have carried out a 5 year follow-up study of a group of 41 originally normotensive (BP less than 160/95 mmHg) newly diagnosed Type 2 (non-insulin-dependent) diabetic patients (26 men, 15 women) and 86 non-diabetic subjects (39 men, 47 women) to assess the predictive value of serum insulin levels with regard to the development of hypertension. Hypertension (BP greater than 160/95 mmHg and/or drug treatment) developed in 14% of diabetic patients and 10% of non-diabetic subjects (NS). The baseline postglucose insulin levels tended to be higher in those diabetic and non-diabetic subjects who developed hypertension during the 5 year follow-up than in those who remained normotensive, and in non-diabetic subjects the differences were statistically significant after adjustment for age, sex and body mass index for the baseline 1 hour serum insulin (104 +/- 18 vs. 68 +/- 5 mU/l; P less than 0.05) and area under the insulin curve (138 +/- 34 vs. 85 +/- 8 mU/l.h, P less than 0.05). Both diabetic and non-diabetic subjects who developed hypertension showed elevated total- and VLDL-triglycerides at baseline compared with those subjects who remained normotensive during the follow-up. In conclusion, the results support the hypothesis that hyperinsulinaemia or insulin resistance may play a role in the pathogenesis of hypertension.     

Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease

BACKGROUND: Advanced glycation end products (AGEs)-receptor (RAGE) axis is implicated in diabetic vascular complication. Since a soluble form of RAGE (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC damage. In this study, we examined whether sRAGE levels were elevated in type 2 diabetic patients compared with non-diabetic healthy subjects. METHODS: Serum sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46 women; mean age 66 +/- 11 years) and 75 age- and sex-matched non-diabetic healthy control subjects. We explored the association between sRAGE levels and coronary artery disease (CAD) in diabetic patients. RESULTS: Serum sRAGE levels were significantly higher in diabetic patients than in non-diabetic subjects (965.3 +/- 544.2 vs 415 +/- 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol, hemoglobin A(1c), and creatinine were significantly associated with sRAGE. After performing multivariate analyses, the presence of diabetes (p < 0.0001) was a sole independent determinant of sRAGE. Furthermore, there was a significant difference in sRAGE levels between diabetic patients with CAD and those without CAD (1680.6 +/- 891.1 vs 855.2 +/- 372.1 pg/mL, p < 0.001). Multiple stepwise regression analysis revealed that sRAGE and creatinine levels were independent determinants of CAD. CONCLUSIONS: The present study demonstrated that serum sRAGE levels were significantly higher in type 2 diabetic patients than in non-diabetic subjects and positively associated with the presence of CAD.     

Endothelial nitric oxide synthase Glu298Asp (G894T) gene polymorphism in coronary artery disease patients with type 2 diabetes mellitus

AimsEndothelial dysfunction is thought to be a significant risk factor for cardiovascular disease. This study determined the role of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism and intergenotypic variation of plasma nitric oxide (NO) levels in coronary artery disease (CAD) patients with type 2 diabetes mellitus (DM).MethodsThis case–control study included 28 documented CAD patients with type 2 DM and 32 non-diabetic patients with CAD. Fifty healthy volunteers without any major cardiovascular risk factors served as controls. NO was estimated by modified Griess method. The eNOS gene polymorphism was studied by amplifying DNA by PCR and digesting with BanII restriction enzyme. Restriction fragment length polymorphism was studied by using a gel documentation system.ResultsThe genotype frequencies for Glu298Asp (GT) genotype were 10.71% in diabetic CAD patients, 28.1% in non-diabetic CAD patients and 12% in controls. The T allele frequency was higher in the non-diabetic CAD group (14%) as compared with the diabetic CAD (5.4%) and control group (6%). NO level was significantly lower in non-diabetic CAD patients (10.25 mmol/L) but not in diabetic CAD patients (13.89 mmol/L) as compared to controls (16.78 mmol/L).ConclusionGlu298Asp polymorphism is not the mediator of increased incidence of CAD in diabetic patients.