High levels of erythrocyte aldose reductase and diabetic retinopathy in NIDDM patients

Summary Erythrocyte aldose reductase was determined in 90 NIDDM patients by a two-site ELISA using recombinant human aldose reductase. The level of aldose reductase did not correlate with age, duration of diabetes, fasting blood glucose and HbA_1cof the patients. Among 38 patients with diabetes for more than 10 years, aldose reductase in those with retinopathy (including non-proliferative and proliferative) was significantly higher than in those without, while no difference in the means of the average HbA_1c, maximum and minimum blood pressure levels was observed between the two groups. The results indicate that the level of aldose reductase in the erythrocyte of diabetic patients is associated with the presence of retinopathy.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - IDDM insulin-dependent diabetes mellitus     

Pre-eclampsia is a potent risk factor for deterioration of retinopathy during pregnancy in type 1 diabetic patients

The aim of the present study was to examine the influence of pregnancy on deterioration of retinopathy in patients with Type 1 diabetes mellitus. Sixty-five pregnant Type 1 diabetic women attending the University Hospital in Lund were studied retrospectively. The degree of retinopathy, and levels of HbA_1c and blood pressure 12 months before, during, and 6 months after pregnancy were compared of those of 56 non-pregnant Type 1 diabetic women matched for age and duration of diabetes. For all patients, sight-threatening deterioration of retinopathy did not differ between the pregnancy group (9/65) and the control group (6/56). Over time, pregnant patients had lower HbA_1c levels than controls (p < 0.001). Pregnant patients with sight-threatening deterioration of retinopathy had higher HbA_1c levels than those without (p = 0.028 and the decrement in HbA_1c between the 6–14th and the 20th week of gestation was more pronounced (p = 0.006). In those patients who developed pre-eclampsia during pregnancy, deterioration of retinopathy ocurred more frequently compared to those without pre-eclampsia (4/8 vs 5/65; p = 0.005). In conclusion, sight-threatening deterioration of retinopathy was not more common during pregnancy in IDDM patients than among age- and duration-matched control patients. In pregnant patients, deterioration of retinopathy was associated with the pregestational degree of metabolic control as well as with a rapidly improved glycaemic control acheived during pregnancy. Among those in whom deterioration occurred during pregnancy, pre-eclampsia was a potent risk factor. © 1997 John Wiley & Sons, Ltd.     

Effects of Insulin on Body Composition in Patients with Insulin-dependent and Non-insulin-dependent Diabetes

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (∼0.6 units kg⁻¹ day⁻¹). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA_1c was greater in IDDM (5.2 ± 0.7 %) than in NIDDM (2.0 ± 0.4 %, p < 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 ± 1.2 vs 3.77 ± 0.5 kg, p < 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 ± 9.3 %) and fat mass in NIDDM (59.9 ± 8.4 %). The increase in lean mass was greater in IDDM than NIDDM (5.6 ± 1.1 vs 1.4 ± 0.3 kg, p < 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 ± 0.8 vs 2.4 ± 0.5 kg, p = ns) and was predominantly an increase in trunk fat (IDDM: 2.3 ± 0.6 kg, NIDDM: 2.0 ± 0.4 kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 ± 0.05 vs 1.09 ± 0.09, p < 0.01) and then increased in IDDM by 0.32 ± 0.15 (p = 0.07) and in NIDDM by 0.22 ± 0.06 (p < 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.     

NIDDM: a rapid progressive disease Results from a long-term,randomised, comparative study of insulin or sulphonylurea treatment

Summary The objective of the present study was to assess the relative efficacy of insulin or glibenclamide treatment for non-insulin-dependent diabetes mellitus (NIDDM) over 42 months. We performed a randomised, controlled trial allocating patients treated with diet and oral antihyperglycaemic agents to treatment with glibenclamide or insulin to achieve HbA_1c levels under 7.5 %. We included 36 subjects with established NIDDM of more than 2 years' duration. Mean HbA_1c levels were significantly reduced in patients allocated to insulin treatment from 9.1 ± 1.4 % before the start to 7.8 ± 1.3 % (p< 0.05) after 1 year, and did not change significantly thereafter throughout the study period. Mean HbA_1c levels increased during the study in the patients allocated to glibenclamide treatment, and 11 of 18 patients had to be switched to insulin treatment due to increasing hyperglycaemia (HbA_1c > 10 %). Mean body weight increased in the subjects allocated to insulin by 7.2 ± 4.1 kg during the study period. In conclusion, insulin was more effective than glibenclamide treatment in obtaining control over hyperglycaemia in these patients, and once improved, glycaemic control did not deteriorate over 42 months in the insulin-treated group. Two thirds of the patients allocated to glibenclamide treatment had to be given insulin due to inadequate glycaemic control. [Diabetologia (1996) 39: 1629–1633]     

The JEVIN trial: A population-based survey on the quality of diabetes care in Germany: 1994/1995 compared to 1989/1990

Summary Since 1990 in most Eastern European countries health care systems have been decentralized or are undergoing the processes of decentralization. Increasingly, diabetic patients are no longer treated by diabetologists but by non-specialized physicians. During the same period structured treatment and teaching programmes have been introduced and health care is increasingly influenced by the St. Vincent declaration. To show the effect of these changes on the quality of diabetes care 90 % (n = 244) of all insulin-treated diabetic patients aged 16 to 60 years and living in the city of Jena (100 247 inhabitants) were studied in 1994/1995. The results were compared with the baseline examination of 1989/1990 (n = 190). HbA_1c (HbA_1c/mean normal) in IDDM patients under specialized care was similar in 1994/1995 (1.54 ± 0.27, n = 47) to 1989/1990 (1.52 ± 0.31, n = 131, p = 0.0018), but higher under non-specialized care (1.71 ± 0.38, n = 80, p = 0.0087). In the total group of NIDDM patients there was no significant change in HbA_1c (1994/1995: 1.75 ± 0.4, n = 117, vs 1989/1990: 1.78 ± 0.4, n = 59, p = 0.67), but with a tendency to higher HbA_1c under non-specialized (1.81 ± 0.4, n = 79) compared to specialized care (1.66 ± 0.39, n = 38, p = 0.06). Incidence of severe hypoglycaemia (IDDM 0.13; NIDDM 0.04), ketoacidosis (0.02; 0.01) and the prevalence of nephropathy (21 %; 35 %) and neuropathy (24 %; 38 %) remained unchanged in comparison to 1989/1990, whereas there was an increase in the prevalence of diabetic retinopathy. Specialized care is mandatory for patients with IDDM. [Diabetologia (1997) 40: 1350–1357] Received: 3 April 1997 and in revised form: 18 June 1997     

Decreased nitric oxide synthase activity in platelets from IDDM and NIDDM patients

Summary Nitric oxide (NO) produced by platelet nitric oxide synthase (NOS) inhibits platelet activation by increased cytoplasmic cGMP levels. The aim of this study was to investigate platelet NOS activity in insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), which are characterized by enhanced platelet activation. HbA_{1 c} levels, platelet NOS and platelet membrane Na⁺/K⁺ ATPase activity were determined in 19 IDDM patients, 21 NIDDM patients and 31 healthy control subjects. NOS activity was measured by a spectrophotometric method based on NO-dependent oxidation of oxyhaemoglobin to met-haemoglobin. Na⁺/K⁺ ATPase activity was measured by the method of Kitao and Hattori. Both NOS and Na⁺/K⁺ ATPase activity were significantly reduced in diabetic subjects compared with control subjects. NOS showed a significant negative relation with HbA_{1 c} levels and a positive relation with Na⁺/K⁺ ATPase activity in diabetic patients. It is hypothesized that the decreased NOS activity might play a role in the pathogenesis of diabetic vascular complications. [Diabetologia (1998) 41: 101–104] Received: 30 June 1997 and in revised form: 3 September 1997     

Long-term intensive insulin therapy in IDDM: effects on HbA1c,risk for severe and mild hypoglycaemia,status of counterregulation and awareness of hypoglycaemia

Summary The present studies were designed to assess the percentage of HbA_1c, frequency, and awareness of hypoglycaemia (H) during long-term intensive therapy (IT) of insulin-dependent diabetes mellitus (IDDM). From 1981 to 1994, 112 IDDM patients were on IT. HbA_1c was 7.17±0.16% (non-diabetic subjects 3.8–5.5%), the frequency of severe H 0.01±0.009 episodes/patient-year, frequency of mild symptomatic H 35.6±2.9 episodes/patient-year. IDDM patients with HbA_1c 5.5% (Group I, n=10), between 6.1–7.0% (Group II, n=12), and 7.6% (Group III, n=11) were studied to assess responses of counterregulatory hormones, symptoms and cognitive function during experimental, stepped H. Compared to 18 non-diabetic subjects, Group I exhibited high thresholds (plasma glucose had to decrease more than normal to evoke responses), and impaired responses of adrenaline, unawareness of H and delayed onset of cognitive dysfunction at the lowest glycaemic plateau (2.3 mmol/l). Group II had normal thresholds and responses, whereas Group III had low thresholds. Frequency of mild H was higher in Group I (54.5±1.9 episodes/patient-year) than in Group II and III (33.7±3.5 and 20.4±2.5 episodes/ patient-year, respectively, p<0.001) and correlated with percentage of HbA_1c (r=–0.82). In conclusion: IT can maintain near-normal HbA_1c and is compatible with low frequency of severe H. However, if HbA_1c is less than 6.0%, mild, symptomatic H is excessively frequent and causes impaired counterregulation and H unawareness. Efforts should be made not only to maintain HbA_1c 7.0%, but also to prevent, recognize and reverse iatrogenic H unawarenes during long-term IT of IDDM by maintaining HbA_1c>6.0%.Abbreviations IDDM Insulin-dependent diabetes mellitus - DCCT Diabetes Control and Complications Trial     

Adherence to a Mediterranean diet and glycaemic control in Type 2 diabetes mellitus

Aims Mediterranean‐type diets reduce the risk of Type 2 diabetes. Whether a Mediterranean‐type diet improves glycaemic control in diabetes remains unknown. Methods We conducted a cross‐sectional analysis in 901 outpatients with Type 2 diabetes attending diabetes clinics located in Campania County, South Italy. We explored the relation between glycated haemoglobin (HbA_1c), measured centrally, self‐measured pre‐ and postprandial glucose levels and consumption of a Mediterranean‐type diet. Adherence to a Mediterranean‐type diet was assessed by a 9‐point scale that incorporated the salient characteristics of this diet (range of scores, 0–9, with higher scores indicating greater adherence). The study was conducted from 2001 to 2007. Results Diabetic patients with the highest scores (6–9) had lower body mass index and waist circumferences, a lower prevalence of the metabolic syndrome and lower HbA_1c and post‐meal glucose levels than diabetic patients with the lowest scores (0–3). In multivariate analysis, mean HbA_1c and 2‐h post‐meal glucose concentrations were significantly lower in diabetic patients with high adherence to a Mediterranean‐type diet than those with low adherence [difference: HbA_1c 0.9%, 95% confidence intervals (CI) 0.5–1.2%, P < 0.001; 2‐h glucose 2.2 mmol/l, 95% CI 0.8–2.9 mmol/l, P < 0.001]. Conclusions In Type 2 diabetes, greater adherence to a Mediterranean‐type diet is associated with lower HbA_1c and postprandial glucose levels.     

Relation of fibre intake to HbA1c and the prevalence of severe ketoacidosis and severe hypoglycaemia

Summary The effect of dietary fibre intake on glycaemic control is still controversial. This study analysed the intake of natural dietary fibre in patients with Type I diabetes mellitus enrolled in the EURODIAB IDDM Complications Study to determine any associations with HbA_1c levels and with the prevalence of severe ketoacidosis or severe hypoglycaemia. Dietary intake was assessed by a 3-day dietary record. The relation between intake of fibre (total, soluble and insoluble) and HbA_1c was examined in 2065 people with Type I diabetes. Associations with severe ketoacidosis (requiring admission to hospital) and severe hypoglycaemia (requiring the help of another person) were analysed in 2687 people with Type I diabetes. Total fibre intake (g/day) was inversely related to HbA_1c (p = 0.02), independently of carbohydrate intake, total energy intake and other factors regarding lifestyle and diabetes management. Severe ketoacidosis risk fell significantly with higher fibre intake (p = 0.002), with an adjusted odds ratio of 0.48 (95 % confidence interval 0.27 to 0.84) in the highest quartile ( ≥ 23.0 g fibre/day) compared with the lowest quartile ( ≤ 13.7 g fibre/day). The occurence of severe hypoglycaemia was not related to fibre intake. Beneficial effects of fibre on HbA_1c and the risk of severe ketoacidosis were particularly pronounced in patients from southern European centres. This study shows that higher fibre intake is independently related to a reduction in HbA_1c levels in European people with Type I diabetes. Furthermore, increased fibre intake may reduce the risk of severe ketoacidosis. These beneficial effects were already observed for fibre intake within the range commonly consumed by people with Type I diabetes. [Diabetologia (1998) 41: 882–890] Received: 31 December 1997 and in revised form: 5 March 1998     

Lens autofluorescence is increased in newly diagnosed patients with NIDDM

Summary Lens and cornea autofluorescence has been shown to be increased in patients with insulin-dependent diabetes mellitus and to be positively correlated to glycaemic control and duration of diabetes. We have studied lens and cornea autofluorescence at the clinical onset of non-insulin-dependent diabetes mellitus (NIDDM), in comparison with age-matched subjects with normal glucose tolerance. Fourteen subjects with NIDDM diagnosed less than 6 months prior to the examination were characterised by ocular fluorometry, glycosylated hemoglobin A_1c, plasma lipid status, arterial blood pressure, and an oral glucose tolerance test (OGTT). Eleven age- and gender-matched healthy subjects without a family history of diabetes and with a normal glucose tolerance underwent the same examinations. In 11 of the 14 diabetic patients lens autofluorescence was increased to levels higher than the age-related mean + 2 SD of healthy subjects. For the entire study population, control and diabetic subjects, lens fluorescence was positively correlated with HbA_1c (p < 0.0001, r = 0.73), fasting plasma glucose (p = 0.002, r = 0.60) and the plasma glucose level 2 h after an OGTT (p = 0.004, r = 0.55). Cornea autofluorescence was also significantly increased in the group of newly diagnosed NIDDM patients, but only 9 patients had values above the mean + 2 SD of the healthy subjects. NIDDM could be detected by ocular fluorometry with a sensitivity of 79 % and a specificity of 100 %. We conclude that lens and cornea autofluorescence is abnormally increased in the majority of patients with newly diagnosed NIDDM. The sensitivity and specificity of the method indicate that lens fluorometry may potentially be useful for screening for undiagnosed NIDDM in the general population. Additionally, we propose that the method may be a clinically useful indicator of cumulative glycaemia and risk of development of secondary complications in patients with diabetes. [Diabetologia (1996) 39: 1524–1527] Received: 28 June 1996 and in revised form: 24 September 1996     

Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control

Summary The adhesion of leucocytes to the endothelium, an early step in atherogenesis, is mediated by cell adhesion molecules. In this study we evaluated the concentration of soluble adhesion molecules in patients with insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) and studied its relation to glycaemic control. Soluble adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were measured in 31 diabetic patients (18 with IDDM and 13 with NIDDM), 20 hyperlipoproteinaemic patients (10 with type IIa and 10 with type IIb) and 20 healthy subjects. Increased E-selectin concentrations were found in the patients with IDDM and NIDDM and in the hyperlipoproteinaemic patients when compared to the control subjects (p<0.01 for all the groups). ICAM-1 was found to be elevated only in the patients with NIDDM (p<0.01). No significant differences in VCAM-1 concentration were found in the different groups of subjects. The concentration of plasma E-selectin was positively correlated with the glycated haemoglobin (r=0.54, p<0.01) in patients with IDDM and NIDDM. In the same patients E-selectin was not related to the concentrations of plasma lipids in spite of the fact that it was found to be elevated in hyperlipoproteinaemic subjects. The results though preliminary suggest that in diabetic patients the concentration of soluble adhesion molecules and especially of E-selectin may be related to metabolic control.Abbreviations IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - ICAM-1 intercellular adhesion molecule-1 - VCAM-1 vascular adhesion molecule-1 - AGE advanced glycation end products     

Evaluation of risk factors for the development of nephropathy in patients with IDDM: insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control

Summary Diabetic nephropathy represents a major complication in patients with insulin-dependent diabetes mellitus (IDDM). Intervention trials using angiotensin-converting enzyme (ACE) inhibitors have pointed towards the important pathogenetic role of the renin-angiotensin system. Recently an insertion/deletion (I/D) polymorphism for the gene encoding the ACE has been described, the deletion type being associated with higher plasma ACE levels. As the intrarenal renin-angiotensin system might also be activated in this setting, we determined the ACE genotype together with other risk factors for the development of diabetic nephropathy in 122 patients with IDDM from a single centre with (n = 63) and without (n = 59) nephropathy. Long-term glycaemic control was evaluated using mean HbA_1c values from the last 10 years. The two patient group were comparable with regard to duration of diabetes and glycaemic control as assessed by current HbA_1c values. However, mean long-term HbA_1c values were significantly higher in patients with diabetic nephropathy as was systemic blood pressure. The DD genotype was more prevalent in patients with renal disease. In the subgroup of patients who had had diabetes for more than 20 years (n = 90), the DD genotype was even more frequent in patients with nephropathy, and blood pressure and long-term HbA_1c values were also higher in patients with renal disease. Logistic regression analysis revealed long-term glycaemic control, blood pressure and the ACE genotype to be independent risk factors for the prevalence of diabetic nephropathy. [Diabetologia (1997) 40: 327–331] Received: 1 July 1996 and in final revised form: 20 November 1996     

The Effect of Glycaemic Control and the Introduction of Insulin Therapy on Retinopathy in Non-insulin-dependent Diabetes Mellitus

To study the progression of diabetic retinopathy in relation to diabetes treatment and glycaemic control in patients with non-insulin dependent (Type 2) diabetes mellitus (NIDDM), we performed a prospective study in a cohort of 1378 diabetic patients, aged ⩾40 years at diagnosis, of whom 333 were treated with insulin, and 1045 with oral antihyperglycaemic agents or diet alone. In the latter group 174 patients changed to insulin therapy during follow-up. We used the Wisconsin scale to grade retinopathy, recorded blindness (visual acuity ⩽0.1) and visual impairment (visual acuity 0.2–0.4), and measured the average HbA_1c for each patient during a mean 3.1-year study period. In a multivariate analysis, patients who changed treatment from oral agents or diet alone to insulin therapy had a relative risk of 2.0 (95 % confidence interval 1.7–2.3) for progression of retinopathy ⩾3 levels compared with all other patients in the study. The increase in risk remained even after controlling for mean HbA_1c (relative risk 1.6; 95 % confidence interval 1.3–1.9). Progression ⩾3 levels was significantly associated with a higher incidence of macular oedema and deterioration of visual acuity (p < 0.001). The relative risk for blindness/visual impairment due to retinopathy was 2.7 (95 % confidence interval 1.8–4.0) in the group with changed treatment compared with all the other patients in the study. Poor glycaemic control (HbA_1c %) before the start of insulin therapy and any retinopathy at baseline were significant risk factors for progression in the group with changed treatment (both p < 0.01). In the whole study group, poor glycaemic control was significantly associated with retinopathy progression ⩾3 levels; the relative risk for those having mean HbA_1c above the median being 1.7 (95 % confidence interval 1.4–2.1), compared to those with a HbA_1c value below the median. Moderate non-proliferative diabetic retinopathy at baseline was also associated with progression (relative risk 2.5; 95 % confidence interval 1.4–4.5). In contrast, insulin treatment at baseline was not associated with an increased risk of retinopathy progression. In conclusion, while hyperglycaemia was a risk factor for the progression of retinopathy in all patients, change of treatment from oral drugs to insulin was associated with a 100 % increased risk of retinopathy progression and a 3-fold increased risk of blindness/visual impairment. © 1997 by John Wiley & Sons, Ltd.     

Low Prevalence of Microalbuminuria in Young Italian Insulin-dependent Diabetic Patients with Short Duration of Disease: a Population-based Study

Objectives of this study were to determine the prevalence of microalbuminuria and the level of glycaemic control obtained in a young Italian population-based cohort of subjects with short duration of insulin-dependent diabetes mellitus (IDDM). Out of 298 subjects with onset of IDDM in the period 1984–88, 211 were examined (71 %) in 1991–92 (duration of disease 3–9 years). Microalbuminuria was defined as albumin excretion rate (AER) 20–200 μg min⁻¹ in an overnight urine collection or alb/creat > 2.5 mg mmol⁻¹ in men and >4.5 mg mmol⁻¹ in women in one first morning urine sample. Twelve subjects had AER 20–200 μg min⁻¹ and 4 had elevated alb/creat ratio. Prevalence of microalbuminuria was 7 % (95 % CI 4.0–11.1) in subjects with duration of IDDM 3–9 years and 4 % (0.3–7.7) in subjects with duration 3–5 years. Only 1 microalbuminuric subject was found out of 52 aged ⩽14 years. Duration of IDDM was significantly higher (6.9 ± 1.9 years vs 5.7 ± 1.6, p = 0.007) and HDL-cholesterol lower (1.22 ± 0.21 mM vs 1.42 ± 0.34, p = 0.025) in micro-than in normoalbuminuric subjects, even after adjustment for age, systolic and diastolic blood pressure, BMI, and HbA_1c. In almost 50 % of the cohort, HbA_1c levels were over 9 %, whereas only in 10.9 % HbA_1c levels were lower than 6.6 % (mean + 3 SD). In conclusion, this Italian population-based study showed low prevalence of microalbuminuria in young subjects with short duration of IDDM, even if the glycaemic control obtained was far from ideal.     

Sustained good glycaemic control in NIDDM patients by implementation of structured care in general practice: 2-year follow-up study

Summary In primary care it is difficult to treat the growing number of non-insulin-dependent diabetic (NIDDM) patients according to (inter)national guidelines. A prospective, controlled cohort study was designed to assess the intermediate term (2 years) effect of structured NIDDM care in general practice with and without ’diabetes service' support on glycaemic control, cardiovascular risk factors, general well-being and treatment satisfaction. The ’diabetes service', supervised by a diabetologist, included a patient registration system, consultation facilities of a dietitian and diabetes nurse educator, and protocolized blood glucose lowering therapy advice which included home blood glucose monitoring and insulin therapy. In the study group (SG; 22 general practices), 350 known NIDDM patients over 40 years of age (206 women; mean age 65.3 ± SD 11.9; diabetes duration 5.9 ± 5.4 years) were followed for 2 years. The control group (CG; 6 general practices) consisted of 68 patients (28 women; age 64.6 ± 10.3; diabetes duration 6.3 ± 6.4 years). Mean HbA_{1 c} (reference 4.3–6.1 %) fell from 7.4 to 7.0 % in SG and rose from 7.4 to 7.6 % in CG during follow-up (p = 0.004). The percentage of patients with poor control (HbA_{1 c} > 8.5 %) shifted from 21.4 to 11.7 % in SG, but from 23.5 to 27.9 % in CG (p = 0.008). Good control (HbA_{1 c} < 7.0 %) was achieved in 54.3 % (SG; at entry 43.4 %) and 44.1 % (CG; at entry 54.4 %) (p = 0.013). Insulin therapy was started in 29.7 % (SG) and 8.8 % (CG) of the patients (p = 0.000) with low risk of severe hypoglycaemia (0.019/patient year). Mean levels of total and HDL-cholesterol (SG), triglycerides (SG) and diastolic blood pressure (SG + CG) and the percentage of smokers (SG) declined significantly, but the prevalence of these risk factors remained high. General well-being (SG) did not change during intensified therapy. Treatment satisfaction (SG) tended to improve. Implementation of structured care, including education and therapeutic advice, results in sustained good glycaemic control in the majority of NIDDM patients in primary care, with low risk of hypoglycaemia. Lowering cardiovascular risk requires more than reporting results and referral to guidelines. [Diabetologia (1997) 40: 1334–1340] Received: 5 February 1997 and in revised form: 22 May 1997     

Individual teaching as a first-step intervention for the education of diabetic subjects

Summary The effects of individual teaching imparted during routine diabetologic counselling on the knowledge concerning diabetes and metabolic control, were assessed in 42 outpatients (28 IDDM; 14 NIDDM), attending the diabetic clinic (study group, SG). We evaluated the outcome of a multiple-choice questionnaire and fasting blood glucose (FBG), 24-h urine glucose (UG), mean regulation index (MRI) and glycated hemoglobin (HbA₁), before and 60 days after providing information about diet (D), physical exercise (E) and hypoglycemic drugs (HD) or insulin therapy (IT). Results were compared with those obtained in a group 57 age- and sex-matched patients (36 IDDM; 21 NIDDM) who did not receive individual teaching (control group, CG). Knowledge concerning diabetes at the second evaluation was significantly higher (p<0.001) in SG than in CG for D and IT, although an improvement was observed in all items. SG patients showed a significant improvement of knowledge (p<0.05) for D, a not significant improvement for HD and IT and no change for E. No change was observed for HbA₁, MRI and UG, while a significant decrease (p<0.05) was observed for FBG in SG. At the second evaluation, FBG of SG patients was significantly lower (p<0.05) than that of CG patients. Our results go to show that individual teaching can improve the level of knowledge of patients without affecting metabolic control. Individual teaching during routine diabetologic counselling represents in our opinion an effective and economic educational model. This study was performed within the framework of theRicerca Finalizzata della Regione Toscana. In addition, it was supported in part by grant n-^o 84.02442.56 from the National Research Council (CNR) and by a grant from theMinistero della Pubblica Istruzione (Ricerca Scientifica 1986).     

Lipid Composition of Platelets in Patients with Non-insulin-dependent Diabetes Mellitus: Studies Before and After Treatment of Diabetes

The study was designed to investigate whether impaired composition of platelet lipids in untreated diabetic patients improved after diabetic treatment. Fourteen untreated patients with non-insulin-dependent diabetes mellitus (NIDDM) and 15 healthy control subjects were studied. In the diabetic patients, the ratio of free cholesterol to phospholipid (FC/PL) in platelets of 0.33 ± 0.02 (mean ± SEM) at pre-treatment, which was statistically (p < 0.05) higher than that of 0.26 ± 0.02 in control subjects, was significantly decreased to the value of 0.29 ± 0.02 (p < 0.01) after insulin therapy. Platelet FC level of 9.77 ± 0.77 μg 10^?8 cells pre-treatment was significantly (p < 0.01) reduced to the value of 7.72 ± 0.38 μg 10^?8 cells post-treatment. Platelet PL level showed no significant changes after the treatment. There was a significantly (p < 0.01) positive correlation between the decrease in FC/PL of platelets and that in haemoglobin A_1c (HbA_1c) after treatment for diabetes (rs = ?0.729). These results indicate that the impaired lipid composition in platelets can be improved after an adequate glycaemic control in patients with NIDDM.     

Unchanged gene expression of glycogen synthase in muscle from patients with NIDDM following sulphonylurea-induced improvement of glycaemic control

Summary We have previously shown that the mRNA expression of muscle glycogen synthase is decreased in non-insulin-dependent diabetic (NIDDM) patients; the objective of the present protocol was to examine whether the gene expression of muscle glycogen synthase in NIDDM is affected by chronic sulphonylurea treatment. Ten obese patients with NIDDM were studied before and after 8 weeks of treatment with a weight-maintaining diet in combination with the sulphonylurea gliclazide. Gliclazide treatment was associated with significant reductions in HbA_1c (p=0.01) and fasting plasma glucose (p=0.005) as well as enhanced beta-cell responses to an oral glucose load. During euglycaemic, hyperinsulinaemic clamp (2 mU · kg^–1 · min^–1) in combination with indirect calorimetry, a 35% (p=0.005) increase in whole-body insulin-stimulated glucose disposal rate, predominantly due to an increased non-oxidative glucose metabolism (p=0.02) was demonstrated in the gliclazide-treated patients when compared to pre-treatment values. In biopsies obtained from vastus lateralis muscle during insulin infusion, the half-maximal activation of glycogen synthase was achieved at a significantly lower concentration of the allosteric activator glucose 6-phosphate (p=0.01). However, despite significant increases in both insulin-stimulated non-oxidative glucose metabolism and muscle glycogen synthase activation in gliclazide-treated patients no changes were found in levels of glycogen synthase mRNA or immunoreactive protein in muscle. In conclusion, improved blood glucose control in gliclazide-treated obese NIDDM patients has no impact on the gene expression of muscle glycogen synthase.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - GS glycogen synthase - G6P glucose-6-phosphate - OGTT oral glucose tolerance test - AUC area under the curve - HGO hepatic glucose output - PCR polymerase chain reaction - bp base pair     

Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria

Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18–42 years, with a duration of diabetes of 4–8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min⁻¹ 1.73 m⁻² (equivalent to 2 SD above mean for a control population). Analysis was by paired Student’s t-testing and linear regression. GFR correlated significantly with HbA_1c (r = 0.47, p < 0.0001) and fructosamine (r = 0.24, p = 0.035). Mean HbA_1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA_1c: 9.2 % (95 % C.I. 7.9–10.4 %) vs 7.6 % (7.2–7.9), p = 0.002; fructosamine: 479 μmol l⁻¹ (450–507) vs 410 μmol l⁻¹ (388–432), p = 0.009. This significant difference persisted even when the two highest values of HbA_1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA_1c (r = 0.31, p = 0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM. Copyright © 1998 John Wiley & Sons, Ltd.