Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

Aims/hypothesis. We examined whether endothelial function is impaired in patients with Type I (insulin-dependent) diabetes mellitus under conditions of near-normoglycaemia compared with age-matched healthy control subjects. Our aim was to determine whether microalbuminuria is associated with endothelial dysfunction in Type I diabetes. Methods. Endothelial function, measured as post-ischaemic flow-mediated dilatation of the brachial artery using ultrasound, was compared among 17 microalbuminuric and 17 normoalbuminuric diabetic patients, and 17 control subjects. Glyceryl trinitrate-mediated dilatation of the brachial artery was used to measure endothelium-independent function. All diabetic patients were studied at near-normoglycaemia, using insulin and 5 % dextrose infusions to maintain blood glucose between 3.5 and 8.0 mmol/l. Results. Flow-mediated dilatation was significantly lower in microalbuminuric diabetic patients (3.2 ± 0.3 %) compared with normoalbuminuric diabetic patients (5.4 ± 0.6 %) and control subjects (7.9 ± 0.6 %, p < 0.001). Normoalbuminuric diabetic patients also had significantly lower flow-mediated dilatation than control subjects (p = 0.01). Glyceryl trinitrate mediated dilatation was significantly lower in the microalbuminuric patients compared with the control subjects (11.9 ± 1.1 % vs 20.0 ± 1.2 %, p = 0.001). Albumin excretion rate and glycated haemoglobin showed a significant negative independent correlation with flow-mediated dilatation (both p < 0.05). Conclusion/interpretation. Type I diabetic patients show endothelial dysfunction at near-normoglycaemia compared with the control subjects, and this abnormality is more marked in diabetic patients with microalbuminuria. Endothelial dysfunction in Type I diabetes is related to the albumin excretion rate and glycaemic control. The presence of endothelial dysfunction in normoalbuminuric diabetic patients suggests it could precede microalbuminuria as an early risk marker for cardiovascular disease. [Diabetologia (2001) 44: 593–601] Received: 6 November 2000 and in revised form: 11 January 2001     

Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus

Abstract Aims/hypothesis. The renin-angiotensin system is possibly involved in the pathogenesis of diabetic nephropathy. The most striking change in renin-angiotensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum concentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microalbuminuria. Methods. Patients (n = 199) with Type I (insulin-dependent) diabetes mellitus and normoalbuminuria at baseline were prospectively followed for 10 years. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression analysis. Results. Of the patients 29 developed microalbuminuria. Glycated haemoglobin values were higher at baseline in these patients. Serum prorenin was similar at baseline but rose in the 29 patients before the development of microalbuminuria and was stable in patients with stable albumin excretion. Renin, angiotensinogen and angiotensin converting enzyme serum concentrations were stable in both groups. Prorenin and glycated haemoglobin were independent prognostic factors for the development of microalbuminuria. A prognostic index, based on these variables, was constructed to estimate the relative risk of developing microalbuminuria. Conclusions/interpretation. Increase in serum prorenin precedes onset of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbuminuria. [Diabetologia (1999) 42: 1006–1010] Received: 30 December 1998 and in revised form: 1 April 1999     

Maternal arterial stiffness in pregnancies affected by Type 1 diabetes mellitus

Aim There is little information about maternal central haemodynamics and arterial stiffness in pregnancies affected by Type 1 diabetes mellitus. The aim of the current study was to investigate whether maternal arterial stiffness is altered in pregnant women with Type 1 diabetes mellitus compared with women with uncomplicated pregnancies. Methods This was a cross‐sectional study involving 37 pregnant women without diabetes and 37 pregnant women with Type 1 diabetes mellitus during the second trimester of pregnancy. Maternal wave reflection (augmentation index) and pulse wave velocity of the carotid‐femoral and carotid‐radial part of the arterial tree were assessed non‐invasively using applanation tonometry. Results Pregnant women with normal pregnancies and Type 1 diabetes mellitus had similar augmentation index (3.7 ± 12.8 vs. 5.1 ± 12.6%, P = 0.6), even after adjusting for possible confounders. Within the group of diabetic women, augmentation index was associated with duration of diabetes (P = 0.003, r² = 0.22) but not with glycated haemoglobin. Pulse wave velocities were similar between the two groups of women (carotid‐femoral: 5.6 ± 0.9 vs. 5.7 ± 1.1 m/s, P = 0.4; carotid‐radial: 7.4 ± 1.2 vs. 7.8 ± 1 m/s, P = 0.1). In the diabetic women there was no significant association between the pulse wave velocities and either duration of diabetes or glycated haemoglobin. Conclusions Pregnancy in women with Type 1 diabetes mellitus is not associated with altered maternal systemic arterial stiffness. However, maternal wave reflections increase with the duration of diabetes.     

HbA1c levels and all-cause mortality in type 2 diabetic patients: Epidemiological evidence of the need for personalised therapeutic targets

Background and AimThe aim of the present case-control study is to explore the effect of case mix on the relationship between glycated haemoglobin (HbA1c) and mortality in type 2 diabetic patients.Methods and ResultsA nested case-control study data set was generated from the cohort-study data set (n = 4140 type 2 diabetic outpatients) by sampling controls from the risk sets. Cases (n = 427) were compared with an equal number of controls chosen from those members of the cohort who were at risk for the same follow-up time of the case, matched for age (±3 years), sex, body mass index (BMI) (±2 kg m^?2), duration of diabetes (±5 years), and Charlson's Comorbidity Score (CCS) (±1). The main predefined analysis was the comparison of cases and controls for proportion of patients with each HbA1c class (<6.5%, 6.5–7.4%, 7.5–8.4% and ≥8.5%).During a mean follow-up of 5.7 ± 3.5 years, 427 deaths were recorded. The lowest risk of death was observed in the HbA1c 6.5–7.4% category; a lower HbA1c was associated with a non-significant trend towards a higher risk. The risk associated with a low (<6.5%) HbA1c was significantly greater in patients who were insulin-treated than in the rest of the sample.ConclusionsThe present study suggests that glycaemic targets should be individualised on the basis of the characteristics of each patient, considering age, co-morbidity and duration of diabetes. Caution should be used in prescribing insulin to reach near-normoglycaemia, particularly in older, frail patients.     

Toll-like receptor 2 expression on monocytes and microvascular complications in type 2 diabetic patients

Diabetes mellitus (DM) is a chronic debilitating illness, and atherosclerotic changes are inevitable and usually neglected during the follow-up of diabetic patients. Toll-like receptor 2 (TLR2) is under trial in many studies to hold responsibility for atherosclerosis process progression as they suggest a malfunction of these receptors expressed on monocytes in diabetic patients. This study aimed to assess the association between the TLR2 and type 2 diabetes mellitus (T2DM) in Egyptian diabetic patients and to investigate its relationship with some diabetic complications.MethodsThis study included a 60 diabetic patients group 1 (diabetic complicated), group 2 (diabetic non-complicated) and 30 age-matched normal healthy blood donors.ResultsToll-like receptors (TLRs) expression was significantly associated with T2DM. In this study, the mean fluorescent intensity (MFI) of TLR2 was 596.9 ± 84.78 in group 1, 326.23 ± 62.98 in group 2 while in group 3 it was 208.47 ± 156.73. There was a significant correlation between MFI of TLR2 and random blood sugar (RBS) and glycated haemoglobin (HbA1c) (p < 0.05).ConclusionTLR2 was overexpressed in diabetic patients with microvascular complications compared to diabetic non-complicated patients and normal healthy controls.     

Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus

Aims/hypothesis: Ninety percent of all men with diabetes have Type II (non-insulin-dependent) diabetes mellitus, and erectile dysfunction (ED) is common in this patient group. This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications. Methods: Patients (mean age, 59 years) in this double-blind, placebo-controlled trial were randomised to sildenafil (25–100 mg; n = 110) or matching placebo (n = 109) for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF, score range, 0–5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions. Results: After 12 weeks, the mean scores for questions 3 and 4 had improved significantly in patients receiving sildenafil (3.42 ± 0.23 and 3.35 ± 0.24) compared with placebo (1.86 ± 0.22 and 1.84 ± 0.23; p < 0.0001). Similarly, the GEQ score was higher in the sildenafil (64.6 %) than the placebo group (10.5 %). Even when correlating efficacy with glycated haemoglobin concentrations ( ≤ 8.3 % or > 8.3 %, the median concentration found in this study) or the number of diabetic complications (0 or ≥ 1), the mean scores for the GEQ and questions 3 and 4 from the IIEF remained higher for all the sildenafil groups compared with the placebo groups (p < 0.0001). Conclusion/interpretation: Sildenafil was well-tolerated and effective in improving erectile dysfunction in men with Type II diabetes, even in patients with poor glycaemic control and chronic complications. [Diabetologia (2001) 44: 1296–1301] Received: 20 April 2001 and in revised form: 16 July 2001     

Abnormal sleep patterns in subjects with type II diabetes mellitus and its effect on diabetic microangiopathies: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 20)

To study the prevalence of Abnormal Sleep Patterns (ASPs), gender-wise, in subjects with type II diabetes mellitus and its influence on diabetic microangiopathies. A population-based cross-sectional survey was conducted among 1,414 patients having type II diabetes mellitus. Diabetic retinopathy was graded using stereoscopic digital fundus photography. Neuropathy was assessed by measuring vibration perception threshold using a sensitometer. Nephropathy was diagnosed by the presence of microalbuminuria in the first morning urine sample. ASPs were defined as either short (less than 5?h) or long (more than 9?h) duration of sleep with excessive daytime sleepiness. The Epworth Sleepiness Scale (ESS) score was assessed to note excessive daytime sleepiness; a score of more than 10 was considered as abnormal. The prevalence of ASPs was more in subjects with diabetes than with those without diabetes (14.8 vs. 6.6%) (P?=?0.009), especially in women (15.7 vs. 5.6%) (P?=?0.021). Likewise, the prevalence of short duration of sleep was higher in subjects with diabetes compared to those without diabetes (6.6 vs. 2.2%) (P?=?0.040). The mean age of women subjects with diabetes, having ASPs, was higher than those without diabetes (56.4?±?8.9?years vs. 47.2?±?5.9?years, P?=?0.033). Women subjects with ASPs had a higher risk of diabetic neuropathy on both univariate and multivariate analysis. ASPs are not only related to diabetes but can also influence the microvascular complications arising due to diabetes, particularly diabetic neuropathy. Diabetology and sleep medicine specialists need to work together to prevent the negative interactions between these two groups.     

Diabetes Mellitus and Employment: Survey of a New Zealand Workforce

A cross-sectional survey of a 5670 multiracial New Zealand workforce aged >40 years was used to determine the health status of people with diabetes mellitus in employment. One hundred and two workers (73 men, 29 women) had known diabetes mellitus (prevalence of 1.8%) of whom 91 individuals (89.2%) had Type 2 diabetes. Mean age of diabetic workers was 51.1 ± 5.6 (SD) years and median duration of disease was 5.0 (range 0–51) years. Most subjects were asymptomatic, although only 31.4% of diabetic workers had fasting glucose concentrations and 35.5% had fructosamine concentrations within the mean ± 2SD range of a matched control group. Moreover, 22.5% of diabetic participants had fasting hypertriglyceridaemia and 21.6% had microalbuminuria. Ethnicity (non-European vs European) and lack of insulin therapy were the most important predictors of poor glycaemic control. We advocate more aggressive therapy with insulin and with culturally sensitive education programmes to avert long-term macrovascular complications.     

Ileal brake failure in streptozotocin‐induced diabetic rat

Background: Diabetes mellitus frequently alters gastrointestinal function, but the pathophysiology of the diabetic gut has not been fully elucidated. Our aim was to characterize the enterogastric modulation of gastric emptying in an experimental model of diabetic rat and to determine the putative consequences of impaired regulation on glycaemic control. Methods: Studies were performed in streptozotozin‐induced diabetic and control groups of male Sprague‐Dawley rats. In rats fitted with chronic ileal cannulae, gastric emptying of a peptide meal was measured during ileal infusion of either lipids (ileal brake) or saline. The influence of the ileal brake mechanism on blood glucose levels after oral administration of a glucose solution was also evaluated. Results: Diabetic rats exhibited a precipitous gastric emptying (80%?±?3% versus 57%?±?3% in controls; P?P?P?P?Conclusion: Experimental diabetes impairs the ileal brake mechanism and disturbs gastric emptying. These abnormalities may contribute to difficult glycaemic control.     

Sleep apnoea in children with diabetes mellitus: effect of glycaemic control

Aims/hypothesis. Patients with diabetes mellitus commonly have cardiovascular autonomic dysfunction and an abnormal ventilatory pattern during sleep. Few data are available on these changes in childhood diabetes. We investigated whether young diabetic children with or without diabetic neuropathy have ventilatory dysfunction during sleep and if so, whether these autonomic changes are related to the duration of diabetes and glycaemic control.¶Methods. We studied 25 children with insulin-dependent diabetes mellitus (19 boys, mean age 7.72 ± 1.99 years). All patients were insulin-dependent at diagnosis; blood samples for HbA_{1 c} assay were collected on the morning before testing and at 3-month intervals during the preceding year. Patients and control subjects (20 age-matched healthy children, 15 boys) underwent overnight polysomnography.¶Results. More diabetic patients than control subjects had sleep apnoeas (p = 0.006); apnoeas in patients also lasted longer (p = 0.07). Patients with poorly controlled diabetes had more apnoeas than patients with well–controlled diabetes and than healthy control subjects (p < 0.0001). Respiratory events during sleep correlated significantly with glycaemic control (r = 0.360; p = 0.09) and with the duration of diabetes (r = 0.430; p = 0.04).¶Conclusion/interpretation. We conclude that respiratory control is compromised very early in children with diabetes. These anomalies are closely related to the duration of diabetes and to glycaemic control. In young children with diabetes, screening of ventilatory control using recording techniques that are simpler than polysomnography could provide an early indication that an adverse cardiopulmonary reaction has begun. [Diabetologia (2000) 43: 696–702]     

Significant correlation of glycated albumin, but not glycated haemoglobin, with arterial stiffening in haemodialysis patients with type 2 diabetes

Objective We recently reported that glycated albumin (GA) is a better indicator of glycaemic control compared with glycated haemoglobin (HbA1c) in haemodialysis (HD) patients with type 2 diabetes. As poor glycaemic control is considered an independent risk factor for atherosclerosis in diabetes, the relationship between GA, HbA1c and arterial stiffening was examined in HD patients with type 2 diabetes. Patients and methods The present study comprised 134 HD patients with type 2 diabetes, and 158 patients without diabetes. Brachial‐ankle pulse wave velocity (baPWV) was measured in all patients using a waveform analyser. Results The mean plasma glucose (PG), GA and HbA1c levels were 7·49 ± 2·28 mmol/l, 20·8 ± 5·57% and 5·62 ± 1·26%, respectively, in HD patients with diabetes (n = 134), which were significantly greater than the respective values of 5·77 ± 1·89 mmol/l, 15·6 ± 2·34% and 4·98 ± 0·80% in those without diabetes (n = 158) (P < 0·0001). BaPWV was 21·69 ± 6·90 m/s in HD patients with diabetes, which was significantly greater than the value of 18·74 ± 4·89 m/s in those without diabetes (P < 0·0001). When the analysis was performed in a combined population of those patients with and without diabetes, the mean PG (r = 0·155, P < 0·05) and GA (r = 0·117, P < 0·05), but not HbA1c (r = 0·092, P = 0·125), exhibited significant correlations with baPWV. Multivariate regression analysis, which included age, gender, mean blood pressure, and serum levels of albumin, creatinine and LDL cholesterol, to evaluate the independent association of each marker for glycaemic control with baPWV values in HD patients demonstrated that GA, but not HbA1c or PG, was an independent factor that was significantly associated in a positive manner with baPWV in HD patients. Conclusion It was suggested that poor glycaemic control, as reflected by increased GA values, might be associated with increased arterial stiffening in HD patients.     

Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease

Objectives. To study the changes in autonomic nervous function during the 4-year follow-up period in diabetic patients and to investigate factors predicting autonomic nervous dysfunction Design. A 4-year follow-up study. Setting. At baseline the study subjects without known cardiovascular disease were recruited from a large group of diabetic and nondiabetic subjects selected randomly from a baseline population. Subjects. Middle-aged control subjects (n=44), patients with insulin-dependent diabetes mellitus (n=32) and patients with non-insulin-dependent diabetes mellitus (n=32) were studied at baseline and after the 4-year follow-up. Interventions. Autonomic nervous function tests and exercise test at baseline and after the 4-year follow-up. Results. At the baseline, heart rate variation during deep breathing was significantly lower in patients with insulin-dependent diabetes (13.0±1.2 beats min^?1; P<0.05) and in patients with non-insulin-dependent diabetes (12.9±1.5 beats min^?1; P<0.05) than in control subjects (16.6±1.1 beats min^?1). At baseline, autonomic nervous function score was significantly higher indicating disturbed autonomic nervous function in patients with insulin-dependent diabetes (1.74±0.19; P<0.01) than in control subjects (1.24±0.14), but the difference was not significant between control subjects and patients with non-insulin-dependent diabetes (1.47±0.12). During the follow-up, autonomic nervous function score increased in patients with noninsulin-dependent diabetes to 2.00±0.21 (P<0.001, as compared to baseline), but did not change in patients with insulin-dependent diabetes (1.77±0.18) or control subjects (1.22±0.12). In both diabetic groups, the deterioration of autonomic nervous function score during the 4-year follow-up was associated with poor glycaemic control at baseline. Clinical manifestation of coronary heart disease was found in three (7%) control subjects, 12 (37%; P<0.001) patients with insulin-dependent diabetes and 11 (34%; P<0.01) patients with non-insulin-dependent diabetes mellitus at follow-up examination. Autonomic nervous function was more abnormal in those insulin-dependent diabetic patients with coronary heart disease than those without. Conclusions. During the 4-year follow-up the impairment in autonomic nervous function occurred mainly in patients with noninsulin-dependent diabetes. Poor glycaemic control appears to be an important determinant of the progression of autonomic nervous dysfunction in diabetes.     

Random Blood Glucose Estimation in Type 2 Diabetes: Does it Reflect Overall Glycaemic Control?

The relationship between clinic-measured random blood glucose and glycated haemoglobin was investigated in 204 non-insulin-dependent diabetic patients to determine the value of random blood glucose on management decisions in these patients. Treatment was with diet alone in 104 patients (51%: Group 1), and diet and oral hypoglycaemic agents in 100 patients (49%: Group 2). Random blood glucose and glycated haemoglobin were lower in Group 1 than Group 2 (10.9 ± 4.0 vs 13.0 ± 4.0 mmol l^?1, p < 0.001, and 8.5 (7.8–10.2) vs 9.6 (8.1–11.0)%, p < 0.01, respectively), and there was a positive correlation between random blood glucose and glycated haemoglobin in both groups (r_Group1 = 0.76, and r_Group2 = 0.54, both p < 0.001). In Group 1, 48 (46%) patients had a random blood glucose < 10 mmol l^?1 and all but 2 of these had a glycated haemoglobin of < 10%. Thus, random blood glucose < 10 mmol l^?1 was 96% sensitive for glycated haemoglobin < 10%. In Group 2 the same sensitivity was 92%. These data suggest that clinic-measured random blood glucose levels below 10.0 mmol l^?1 predict acceptable overall glycaemic control in non-insulin-dependent diabetic patients, particularly in those on diet alone. However, a clinic-measured random blood glucose above 10 mmol l^?1 was of limited value in predicting glycated haemoglobin values above 10% and a blood glucose cut-off of 14 mmol l^?1 appeared more useful. Where resources are limited, clinic random blood glucose estimation may allow clinicians to use glycated haemoglobin measurements more discriminately.     

Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus

Aims

To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese.

Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – A post-hoc analysis of the PRIORITY randomized clinical trial

AimsBaseline diabetic retinopathy (DR) and risk of development of microalbuminuria, kidney function decline, and cardiovascular events (CVEs) in type 2 diabetes.MethodsPost-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. DR diagnosis included non-proliferative and proliferative abnormalities, macular oedema, or prior laser treatment. Cox models were fitted to investigate baseline DR presence with development of persistent microalbuminuria (urinary albumin-creatinine ratio > 30 mg/g); chronic kidney disease (CKD) G3 (eGFR <60 ml/min/1.73m²); and CVE. Models were adjusted for relevant risk factors.ResultsAt baseline, 304 (17.3 %) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p < 0.001), and higher HbA_1c (62 ± 13 vs. 56 ± 12 mmol/mol, p < 0.001). The adjusted hazard ratios of DR at baseline for development of microalbuminuria (n = 197), CKD (n = 166), and CVE (n = 64) were: 1.50 (95%CI: 1.07, 2.11), 0.87 (95%CI: 0.56, 1.34), and 2.61 (95%CI: 1.44, 4.72), compared to without DR.ConclusionsPresence of DR in normoalbuminuric type 2 diabetes was associated with an increased risk of developing microalbuminuria and CVE, but not with kidney function decline.     

The Natural Course of Microalbuminuria in Insulin-dependent Diabetes: A 10-year Prospective Study

The purpose of this study was to describe the clinical course in patients followed right from the onset of microalbuminuria to the development of diabetic nephropathy. A 10-year prospective follow-up of 209 consecutive normotensive insulin-dependent diabetic patients with normal urinary albumin excretion (UAE <30 mg 24 h^?1), age 34 (18–50) years and duration of diabetes 17 (10–30) years was performed. Twenty-four-hour urinary albumin excretion was measured every 4 months, glycated haemoglobin and supine blood pressure was measured annually. Two-hundred (96%) patients completed 10 (range 5–10) years follow-up. Twenty-nine (15%) patients developed persistent microalbuminuria (UAE 30–300 mg 24 h^?1). Eight of these have progressed to nephropathy and one had died of diabetic nephropathy. Multiple stepwise logistic regression analysis demonstrated baseline urinary albumin excretion (p = 0.0016) and glycated haemoglobin (p = 0.0014) but not blood pressure as predictors of development of microalbuminuria within the following 10 years. The median annual increase in urinary albumin excretion was 27 (range 17–65)% in the 29 patients developing microalbuminuria. The median duration from onset of microalbuminuria to development of nephropathy was 7 years. The prevalence of patients receiving antihypertensive treatment (BP > 140/90 mmHg) increased from 10% at onset of microalbuminuria to 45% 4 years after onset of microalbuminuria. The prevalence of patients with proliferative retinopathy increased from 7% at onset of microalbuminuria to 28% 4 years after onset of microalbuminuria. The incidence of persistent microalbuminuria in normotensive insulin-dependent diabetic patients is 2% per year, and development of persistent microalbuminuria is a strong predictor of overt nephropathy. Development of hypertension is frequent in the early course of microalbuminuria and treatment modalities for normotensive patients with microalbuminuria are urgently needed.     

Fetal haemoglobin levels in adult Type 1 (insulin-dependent) diabetic patients

Summary Glycated haemoglobin levels (HbA₁ and HbA_1c) are established parameters of long-term glycaemic control in diabetic patients. Depending on the method used, fetal haemoglobin interferes with the assays for glycated haemoglobin. If present in high amounts, fetal haemoglobin may lead to overestimation of glycated haemoglobin levels, and therefore, of average blood glucose concentration in diabetic patients. Glycated (HbA_1c) and fetal haemoglobin levels were measured by high pressure liquid chromatography in 60 (30 female) adult Type 1 (insulin-dependent) diabetic patients of Swiss descent, and were compared with levels obtained from 60 normal, non-diabetic control subjects matched for age and sex. Fetal haemoglobin levels were significantly higher in the diabetic patients (0.6±0.1%, mean±SEM; range: 0–3.6%) than in the control subjects (0.4±0.1%, p<0.001). Elevated fetal haemoglobin levels (0.6%) were found in 23 of 60 diabetic patients (38%) compared to 9 of 60 control subjects (15%; ²=8.35, p<0.01). In addition, fetal haemoglobin levels in diabetic patients are weakly correlated with glycated haemoglobin (HbA_1c) (r=0.38, p<0.01). Fetal haemoglobin results were confirmed with the alkali denaturation procedure, and by immunocytochemistry using a polyclonal rabbit anti-fetal haemoglobin antibody. A significant proportion of adult patients with Type 1 diabetes has elevated fetal haemoglobin levels. In certain patients this may lead to a substantial over-estimation of glycated haemoglobin levels, and consequently of estimated, average blood glucose levels. The reason for this increased prevalence of elevated fetal haemoglobin remains unclear, but it may be associated with poor glycaemic control.Presented in part at the 59th Annual Meeting of the Swiss Society of Internal Medicine, Lugano, 1991 and at the 14th International Diabetes Federation Congress, Washington, 1991     

Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in Type I diabetic patients

Aims/hypothesis. Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C¹¹⁶⁶-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three polymorphisms in the genes coding for AGTR1 (A¹¹⁶⁶→C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore, we investigated the relation between a random measurement and long-term measurements of haemoglobin A_{1 c} (HbA_{1 c}).¶Methods. We studied Caucasian patients with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74 women, age 41.1 ± 9.6 years, diabetes duration 28 ± 8 years) and long-standing Type I diabetic patients with persistent normoalbuminuria (112 men 69 women, age 42.5 ± 10.0 years, diabetes duration 27 ± 9 years). Genotyping was PCR-based and metabolic control estimated from all measurements of HbA_{1 c} done in each patient [average (range) n = 31 (6–74)]. The median observation time (range) was 13.5 (2–14) years.¶Results. Type I diabetic patients with a history of poor glycaemic control (HbA_{1 c} above the median, 8.7 %) had an increased risk of diabetic nephropathy compared with patients with a better metabolic control, OR (95 % CI): 9.2 (5.8–14.7). The magnitude of this risk was similar in carriers and non-carriers of the mutations. The risk of nephropathy in patients with HbA_{1 c} above compared with below the median in carriers of the mutant C¹¹⁶⁶-allele, D-allele, or T235-allele were 7.6 (95 % CI: 3.9–14.8), 10.4 (6.0–17.8) and 9.8 (5.4–17.9), respectively. A significant correlation (r = 0.74, p < 0.001) existed between a random and long-term measurements of HbA_{1 c} with a small mean difference (limits of agreement) [0.2 (–1.8 to 2.1) %] between the two estimates.¶Conclusion/interpretation. Poor metabolic control is a major risk factor for diabetic nephropathy in Caucasian Type I diabetic patients. This risk was similar in carriers and non-carriers of the mutant alleles of the AGTR1(A¹¹⁶⁶→C), ACE/ID and angiotensinogen-M235T polymorphisms. The HbA_{1 c} value measured at random reflects rather closely average long-term HbA_{1 c} values. [Diabetologia (2000) 43: 794–799]     

Good glycaemic control reduces oxidation and glycation end-products in collagen of diabetic rats

Summary Blood glucose control plays a prominent role in the aetiology of diabetic complications. Recent data support the hypothesis that non-enzymatic pathways (glycation and oxidation) are involved in the pathogenesis of tissue damage in diabetes mellitus. In this study the level of pentosidine, a marker of glycation, and the intensity of collagen-linked fluorescence glycation (370/440 and 335/385 nm) and oxidation-related (356/460 and 390/460 nm), have been examined in spontaneously diabetic rats with good and poor glycaemic control. Pentosidine increased dramatically in rats with poor control, and slightly in those with good control. At the end of the study, after 6 months of diabetes, pentosidine levels were 13 ± 5 and 2.1 ± 0.5 pmol/mg collagen, respectively (control rats: 1.1 ± 0.1 pmol/mg collagen). A similar pattern was observed for both glycation or oxidation-related fluorescence. The group of rats with poor control always showed elevated average values when compared to rats with good control, with a relative increase of over 200 %. The results emphasize the role of good glycaemic control in preventing the growth of glycation or oxidation end-products in collagen. On comparison between the general mean level of all glycated haemoglobin and the mean pentosidine level of the three groups, a very good exponential correlation was found (r = 0.993, p < 0.001). The fluorescence values presented a less strong relationship, but a correlation with glycaemic control was still present. If the post-translational modifications of proteins play a leading role in the pathogenesis of complications it is possible to conclude that strict glycaemic control, obtained by accurate insulin therapy can prevent them by inhibiting the non-enzymatic modification of proteins and delaying their accumulation in collagen. The therapeutic implications are obvious. [Diabetologia (1996) 39: 1440–1447] Received: 23 March 1996 and in final revised form: 29 August 1996     

Are elderly patients with diabetes being overtreated in French long-term-care homes?

AimIn France, diabetes prevalence and ageing of the population are both on the increase, yet little information on diabetes in elderly patients living in geriatric institutions is available. Moreover, institutionalized diabetic patients are not included in the French recommendations for the management of diabetes in the elderly. For this reason, the aim of the present study was to evaluate diabetes management in older, institutionalized patients.MethodsThe medical records of 100 diabetic patients, aged 65 years and over, and living in seven geriatric institutions in the Côte d’Or region of France, were studied from May 2008 to January 2009.ResultsPrevalence of diabetes in these seven geriatric institutions was 15.46 ± 4.9%, higher than in the general population. The diabetic patients had a mean age of 81.85 ± 11.93 years, and 32% had glycated haemoglobin (HbA_1c) less or equal to 6.5%, indicating a high risk of severe hypoglycaemia. A diet for diabetes was prescribed in 54% of the patients, but HbA_1c levels did not differ between patients following and not following the diet (7.26 ± 1.36% vs 7.11 ± 1.10%, respectively; P = 0.27). Creatinine was assessed in 87% of the patients, and 16% were ophthalmologically followed-up. Daily capillary blood glucose monitoring was performed in 100% of the patients taking insulin and in 17% of those taking oral antidiabetic treatment (P < 0.0001).ConclusionOur data show that, among older institutionalized patients, the prevalence of diabetes is high and the control of diabetes too tight, with a potential risk of hypoglycaemia. Antidiabetic treatment should be reduced when the HbA_1c value is less than 7.5% in this frail and functionally dependent population. Furthermore, a diabetic diet, prescribed for more than half this population, is useless for glycaemic control and may even impinge on quality of life.