A comparison of glycaemic and metabolic control over time among South Asian and European patients with Type 2 diabetes: results from follow-up in a routine diabetes clinic.

AIMS: Although South Asians have a higher prevalence of diabetes which develops at a younger age, data on change in metabolic parameters post-diagnosis are relatively sparse. We therefore wished to determine whether South Asians with diabetes had similar or greater year-on-year deterioration in metabolic parameters compared with Europeans. METHODS: We analysed longitudinal change in metabolic parameters [glycated haemoglobin (HbA(1c)), blood pressure, body mass index (BMI), lipids] among South Asian (n = 210) and European (n = 1557) patients consecutively attending the same diabetes clinic over a mean period of 5.3 years. RESULTS: South Asians were younger than Europeans at first recorded diagnosis of diabetes (mean age 45.9 vs. 57.3 years, P < 0.001) and had significantly lower ( approximately 1.2 units) BMI and blood pressure. Mean HbA(1c) was not different across ethnic groups at first visit, but with time glycaemic control was worse in South Asians than Europeans, with average deterioration 1.31% (= 0.23%/year) in Asians vs. 0.82% (0.16%/year) in Europeans, P = 0.003. This ethnic difference in mean change in HbA(1c) persisted after adjustment for age, sex, baseline HbA(1c), and weight change in linear regression analysis (beta = 0.46, 95% CI 0.24-0.69, P < 0.001), and with additional adjustment for time to referral and duration of diabetes (P = 0.01). Moreover, South Asians had significantly smaller improvements in blood pressure (P < 0.001) and cholesterol (P = 0.044) over the follow-up period in keeping with fewer prescriptions of anti-hypertensive agents and lipid-lowering agents. CONCLUSIONS: These data suggest the need to be more aggressive in the management of diabetes and related risk factors in South Asians.

Enhanced albuminuric response to atrial natriuretic peptide in normoalbuminuric patients with Type 1 diabetes mellitus--a pilot study.

AIMS: To ascertain whether intravenous infusion of atrial natriuretic peptide (ANP) can induce microalbuminuria in patients with Type 1 diabetes mellitus (DM), as already demonstrated in patients with microalbuminuria, and to compare the albuminuric response to ANP infusion in Type 1 DM and a matched group of healthy non-diabetic controls. METHODS: Eight normoalbuminuric DM patients participated in a three limb, randomized, double-blind, placebo-controlled study. Subjects were kept euglycaemic by insulin infusion, and subsequently water-loaded (20 ml/kg orally plus urinary losses). When in steady state, a 30-min infusion of either placebo, ANP 0.025 mg x kg(-1).min(-1) or ANP 0.05 mg x kg(-1) x min(-1) was administered intravenously. Urine was collected every 15 min for 90 min for the estimation of albumin-creatinine ratio (ACR). In addition, eight nondiabetic volunteers received a single infusion of ANP 0.025 mg x kg(-1) x min(-1). RESULTS: ACR was unaltered by placebo in DM subjects (1.4 +/- 0.7-1.7 +/- 1.1 mg/mmol, mean +/- SD, ANOVA, P > 0.9), and by low dose ANP in controls (1.4 +/- 0.9-2.6 +/- 1.9 mg/mmol, P = 0.4). ACR increased with low dose ANP (1.3 +/- 0.5-14.6 +/- 13.6 mg/mmol, P = 0.02), and high dose ANP (1.3 +/- 0.7-26.4 +/- 31 mg/mmol, P = 0.01) in DM subjects. The ACR response to low dose ANP was greater in the DM than control subjects (P = 0.02). CONCLUSIONS: ANP increases urine albumin excretion rate in normoalbuminuric Type 1 DM patients, and this effect is more pronounced than in healthy volunteers.

Angiotensin-converting enzyme inhibition by quinapril blocks the albuminuric effect of atrial natriuretic peptide in Type 1 diabetes and microalbuminuria.

AIMS: This study examined the effect of angiotensin-converting enzyme inhibition, administered at doses with no effect on systemic blood pressure, on the albuminuric action of atrial natriuretic peptide (ANP). METHODS: Seven Type 1 diabetic patients with established microalbuminuria participated in a two limb, single-blind, placebo controlled study. Subjects were administered quinapril 10 mg daily or placebo for 7 days prior to study. On the study day, subjects were euglycaemic clamped and subsequently fluid loaded (20 ml/kg tap water orally plus urinary losses). At steady state diuresis, a 1 h intravenous infusion of ANP 0.05 mg.kg(-1) x min(-1) was administered. Urine was collected at 15-min intervals for estimation of albumin-creatinine ratio (ACR). Results were analysed by ANOVA. RESULTS: Baseline mean arterial pressure was similar after pre-treatment with quinapril and placebo (98.7 +/- 3.8 vs. 100 +/- 4.5 mmHg, mean +/- SD, P > 0.5), and was unaltered by ANP infusion on either study day. Baseline ACR was similar on quinapril and placebo (P = 0.13). ANP infusion induced a rise in urine ACR with placebo (58.4 +/- 40.2 to 393.6 +/- 262.9 mg/mmol, P = 0.006), but not with quinapril (29.3 +/- 10.7 to 81.5 +/- 43 mg/mmol, P = 0.15). The urine ACR response to ANP infusion was higher with placebo than with quinapril (P = 0.02). CONCLUSIONS: Quinapril blocks the albuminuric effect of intravenous infusion of ANP in subjects with Type 1 diabetes mellitus and established microalbuminuria. This action is independent of changes in mean arterial pressure and creatinine clearance.

Socio-economic status and membership of the British Diabetic Association in Scotland.

Socio-economic status is an important predictor of mortality and morbidity in the diabetic and non-diabetic population. Improving the representation of people from deprived areas in vocal pressure groups may foster practical ideas which would improve health outcome. The general public may be represented through a variety of local and national organizations. The British Diabetic Association (BDA) represents people with diabetes mellitus, their relatives, and their health care professionals. Assuming a uniform diabetes prevalence of 1.5%, there would be 75484 diabetic people in Scotland, of which only 5649 (7.5%) are currently members of the BDA. Using area based codes of socio-economic status, it was calculated that the odds ratios of BDA membership in the most affluent category (1) to the most deprived category (7) were 1.00, 0.81, 0.68, 0.57, 0.45, 0.43 and 0.21, respectively (p < 0.00001). Studies reporting on patient cohorts derived from the BDA membership files will include a higher proportion of patients from the most affluent categories, thus, these studies may underestimate overall morbidity and mortality. By promoting membership in the deprived categories it may be possible to develop a clearer picture of diabetes mellitus and new ideas which would help to narrow the health divide.

Metformin treatment in NIDDM patients with mild renal impairment.

Metformin is contraindicated in patients with renal failure because of the risk of lactic acidosis. This study assessed the complications of metformin treatment in patients with non-insulin-dependent diabetes mellitis with normal and raised serum creatinine. Subjects using metformin with serum creatinine above the upper reference range (120 mu mol/l) were identified (n = 17) from a hospital diabetes register; those with abnormal liver function, cardiac failure, peripheral vascular disease or recent severe illness were excluded. Reference plasma lactate levels were established, mean 1.742 mu mol/l (SD 0.819) using age-matched non-diabetic subjects. Age-matched patients treated with metformin with normal serum creatinine levels formed the control group (n = 24). Details of gastrointestinal disturbance were recorded, and plasma lactic acid and vitamin B12 levels measured. The median total daily dose of metformin in both groups was 1700 mg. The mean plasma lactate in subjects with serum creatinine 80-120 mu mol/l (2.640 mmol/l (SD 1.434) p < 0.02) was higher than non-diabetic control levels while diabetic subjects with serum creatinine 120-160 mumol/l had a mean of 2.272 mmol/l (SD 0.763) p < 0.05. There was no significant difference between the two groups taking metformin, nor any significant difference in the reporting of gastrointestinal symptoms between the groups on metformin (11.76% vs 12.5%). Plasma lactic acid levels are higher in diabetic subjects taking metformin compared with healthy volunteers but, within the diabetic groups, the small elevation of serum creatinine was not associated with higher plasma lactate levels.

Socioeconomic status and clustering of cardiovascular disease risk factors in diabetic patients.

OBJECTIVE: Correction of cardiovascular risk factors is an essential component of good diabetes care. Our goal was to examine the relationship of socioeconomic status in five risk factors: obesity, hypertension, high cholesterol, smoking, and high HbA1c. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional prevalence study of all patients with diabetes (n = 1,553) attending a clinic in Glasgow, U.K. Area-based codes were used to measure socioeconomic status; these ranged from 1, the most affluent, to 7, the most deprived. RESULTS: Comparing patients with NIDDM from the seven categories of socioeconomic status, we found that those from deprived categories experienced a higher prevalence of obesity. In the most affluent groups, 30% had a BMI > 30 kg/m2 compared with 47% in the most deprived categories (P < 0.002). With regard to smoking, 13% in the most affluent category smoked compared with 33% in the most deprived (P < 0.001). In patients with IDDM from affluent categories, 13% smoked compared with 34% from deprived categories (P < 0.001). The proportion of patients with no cardiac risk factors fell by 30.6% from deprived category 1 to 7 (P < 0.001), and the proportion of patients with three or more risk factors rose from 8.6% in category 1 to 20.2% in category 7. CONCLUSIONS: Diabetic patients from areas of low socioeconomic status are at increased risk of cardiovascular disease. To counter this, specific health education programs should be evolved and resources should be directed toward these areas.

A study of fluoxetine in obese elderly patients with type 2 diabetes.

In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6-9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.

Metabolic control in diabetic subjects following myocardial infarction: difficulties in improving blood glucose levels by intravenous insulin infusion.

Optimal metabolic control during the first twelve hours after myocardial infarction may be associated with improved survival in diabetic subjects. A comparison of an intravenous insulin infusion regimen aimed at improving blood glucose levels (n = 35), with 'routine control' (n = 34) in the post infarction period has been carried out in diabetic subjects admitted to four Coronary Care Units over a two year period. However, glycaemic control was similar in both groups (intravenous infusion regimen, mean +/- SD capillary blood glucose 10.3 +/- 2.1 mmol/l, 'routine control' glucose 10.7 +/- 3.6 mmol/l). There were no differences in the rates of arrhythmias (31% v 32%), heart failure (46% v 47%) or mortality (17% v 18%). Mortality in diabetic subjects was lower than that quoted in previous studies but was higher than in non-diabetic subjects admitted to the Coronary Care Unit during the same period. Attempts to improve glycaemic control by means of intravenous insulin infusion were unsuccessful.

Comparison of basal and prandial insulin therapy in patients with secondary failure of sulphonylurea therapy.

A group of 35 normal weight patients with secondary failure of sulphonylurea therapy (fasting plasma glucose greater than 8.0 mmol l-1 on maximal dose of sulphonylurea) were randomly assigned to receive either a single injection of a basal insulin supplement (human ultralente insulin, n = 16) or three or four injections of a preprandial insulin supplement (human unmodified insulin, n = 19). Patients performed self-monitoring of capillary blood glucose and adjusted their insulin doses in an effort to achieve fasting and preprandial capillary glucose concentrations of less than 7.0 mmol l-1. Blood glucose control after 16 weeks of insulin therapy was improved to a similar extent by both regimens (HbA1 basal insulin group 12.5 +/- 1.2 (+/- SD) falling to 10.7 +/- 2.2%; preprandial group 12.0 +/- 1.6 falling to 9.5 +/- 1.6%). Preprandial insulin gave better control of daytime blood glucose levels but fasting plasma glucose did not differ between the two regimens (basal group 10.6 +/- 3.6, preprandial group 11.1 +/- 3.6 mmol l-1). Insulin dose was greater in the preprandial group (44.1 +/- 17.9 U day-1) than in the basal group (26.7 +/- 12.5 U day-1 (p less than 0.005), but there was no difference in the frequency or severity of hypoglycaemia between the two treatments. Only the preprandial therapy group showed significant weight gain (2.7 +/- 3.0 kg). While both regimens led to improvement of blood glucose control, these results suggest that neither basal nor preprandial insulin alone can achieve ideal blood glucose control through 24 h in patients with fairly severe failure of control on sulphonylurea therapy.

Vibration perception thresholds in 279 diabetic patients.

Generalised peripheral neuropathy is a well recognised complication of diabetes mellitus and early detection is important in order that morbidity can be reduced by interventional therapy at an early stage. Since nerve conduction studies are not a feasible option in a busy diabetic clinic, an alternative technique of detection, superior to clinical examination, is beneficial. In this study vibration perception thresholds were measured in 279 diabetic outpatients. Seventy-eight patients (28%) had abnormal results but only 35 (13%) had clinical evidence of neuropathy. While nerve conduction studies remain the most sensitive technique to detect nerve dysfunction, vibration perception threshold determination is a useful screening test to detect subclinical peripheral nerve dysfunction in a routine diabetic outpatient clinic.

Continuous 24-hour electrocardiography in thyrotoxicosis before and after treatment.

Ten thyrotoxic individuals, who otherwise had no evidence of cardiovascular disease, underwent continuous ambulatory 24-hour ECG monitoring, before and after antithyroid treatment. The mean age of the subjects was 41 +/- 14.4 years (mean +/- SD) with a range of 22 to 66 years. When subjects were thyrotoxic, the mean heart rate for the group was 104 +/- 10.8 bpm. This fell to 82 +/- 6.8 bpm when the subjects were rendered euthyroid (p less than 0.001). Circadian rhythm of heart rate response was maintained in the thyrotoxic state, although heart rate variability was significantly increased (p less than 0.001). The prevalence of ventricular premature contractions was not significantly different before and after treatment, although premature atrial contractions were more prevalent during the middle third of the day (p less than 0.01) when subjects were euthyroid. These findings support the view that normal adrenergic responsiveness persists in hyperthyroidism, and for most individuals treatment does not significantly alter the prevalence of ectopic activity.

Systolic time intervals in adolescents with insulin-dependent diabetes mellitus.

Systolic time intervals were used to evaluate left ventricular performance in 20 diabetic adolescents with a mean age of 15.2 +/- 2.2 years (range 9-17 years) and were compared with an age- and sex-matched control group. Pre-ejection period index (PEPI), left ventricular ejection time index (LVETI), total electromechanical systole index (QS2I) and the PEP to LVET ratio were calculated at rest and following sustained isometric handgrip (SIHG). None of the diabetics had demonstrable microangiopathy or autonomic neuropathy. There was no significant difference in resting or post-exercise heart rate, PEPI, LVETI or PEP/LVET ratio between the two groups. QS2I was significantly prolonged (p less than 0.05) at rest in the diabetics, but was not significantly different following SIHG. These results indicate that cardiac contractility is not detectably abnormal in young diabetics, compared to their adult counterparts who may develop impaired myocardial performance.

Are insulin dependent diabetics in the West of Scotland prone to nutritional deficiencies?

In a cross-sectional survey, the weight, vitamin and mineral status of 57 insulin dependent diabetics attending a clinic in Glasgow were studied. There were no significant differences in any of the measured parameters between poorly controlled and better controlled diabetics (as assessed by HbA1 status). No gross evidence of nutritional deficiency was found although serum magnesium levels tended to be low. This may be clinically relevant as hypomagnesaemia is associated with cardiac arrhythmias and ischaemic heart disease.

Determination of glycosylated adult and foetal haemoglobins by affinity chromatography.

Estimation of adult glycosylated haemoglobin by affinity chromatography was found to be quick and less dependent on ionic strength, pH and temperature than ion-exchange chromatography. Results obtained by both procedures correlated strongly (r = 0.96) but the range for normal subjects was smaller with the affinity assay. The affinity method correlated equally well with the colorimetric assay (r = 0.95). However, the method did not measure all the glycosylated forms, and only half of the glycosylated species isolated by ion-exchange chromatography was bound to the affinity resin. It also showed that the amount of glycosylated haemoglobin in cord blood is less than in adult blood.

The effects of prolonged bromocriptine administration on PRL secretion GH and glycaemic control in stable insulin-dependent diabetes mellitus.

Plasma glucose, PRL and GH concentrations were measured at hourly intervals over a 24-h period before and after oral bromocriptine administration in a dosage of 7.5 mg/day for 6 weeks in nine stable insulin-dependent diabetic men. The pattern of PRL secretion was noted to be normal in stable diabetes (with a mean concentration of 205 mu/l +/- 23 SEM) and was effectively suppressed by bromocriptine (to a mean concentration of 51 mu/l +/- 2 SEM). This suppression of PRL secretion caused no major alteration in glycaemic control, mean plasma glucose for the group was 10.6 mmol/l +/- 3.4 SD before and 9.6 mmol/l +/- 3.1 SD after bromocriptine administration. Bromocriptine produced no change in plasma glucose or GH profiles. It is concluded that PRL secretion is not a major influence on carbohydrate metabolism in stable diabetics.