Longitudinal screening of serum lipids in children and adolescents with Type 1 diabetes in a UK clinic population

Aims To determine the prevalence of abnormal lipid levels in a large group of children and adolescents with Type 1 diabetes and to examine the changes longitudinally. In addition, to study the relationships of any lipid abnormalities to glycaemic control, age and duration of diabetes. Methods Non‐fasting blood samples were taken annually from all the patients in the Oxford Children's diabetes clinic and total cholesterol (TC), high‐density lipoprotein (HDL) cholesterol, triglycerides (TG) and glycated haemoglobin (HbA_1c) measured over a period of 8 years. Low‐density lipoprotein (LDL) cholesterol and non‐HDL were calculated from these values and compared. Tests performed less than 4 months after diagnosis were excluded. Results A total of 229 children had complete data from more than 1 year and 798 sets of data were examined. TC was lower in males and increased with duration of diabetes and with increasing HbA_1c. HDL cholesterol fell with increasing age, but independently increased with duration, and was not related to HbA_1c. LDL cholesterol and non‐HDL cholesterol were highly correlated (r = 0.9). Both were lower in males and increased with duration of diabetes. Non‐HDL cholesterol increased with HbA_1c. A total of 23.7% had HDL cholesterol < 1.1 mmol/l and 22.5% had TC > 5.2 mmol/l. Thirty‐eight per cent had LDL cholesterol > 2.6 mmol/l and 10.8% > 3.4 mmol/l, the thresholds for lifestyle and drug intervention respectively. Conclusions Abnormalities in plasma lipid levels are common in this age group and the prevalence increases with poor glycaemic control and with duration of diabetes. Around 10% of adolescents would fit criteria for lipid‐lowering medication in adults, but further study is needed to examine the risks and benefits in this age group.     

A multinational,multi‐centre,observational, cross‐sectional survey assessing diabetes secondary care in Central and Eastern Europe (DEPAC Survey)

Aims The objective of this study was to assess diabetes care in outpatient diabetes clinics in the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia and Slovenia. Methods Questionnaires for each randomly enrolled patient were completed by an endocrinologist or diabetologist. Data concerning age, sex, diabetes duration, diabetes type, treatment type, glycated haemoglobin (HbA_1c), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG) and high‐density lipoprotein cholesterol (HDL‐C), blood pressure (BP) and short‐ and long‐term diabetes complications were recorded. Questionnaires were analysed centrally for each country and stratified for Type 1 diabetes (T1D), Type 2 diabetes (T2D) and other types of diabetes. Results Data on 10 950 individuals were analysed (mean population age 56.2 years; females 52%; T1D 22.9%; T2D 75.3%; mean time from diagnosis 11 years). Patients with HbA_1c within target (< 6.5%): T1D 13.1%, T2D 21.4%; for TC levels (< 4.5 mmol/l): T1D 37%, T2D 20%; for TG levels (< 1.7 mmol/l): T1D 78%, T2D 44%; for HDL‐C (> 1.1 mmol/l): T1D 81%, T2D 60%; for LDL‐C (< 2.5 mmol/l): T1D 36%, T2D 23%; for BP (< 130/80 mm Hg): T1D 42%, T2D 9%. The prevalence of severe hypoglycaemia (within the last 6 months) was 12% in T1D and 2% in T2D. Prevalence of diabetic ketoacidosis was 0.3–6.6%, blindness 0.15–1.3% and diabetic nephropathy 19–42%. Conclusions The data show the current quality of care and potential areas for improvement. The quality of care is generally comparable with that in Western Europe.     

A long‐term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized,double‐blind,parallel‐group comparison trial

Aims This study compared the effects of pioglitazone and gliclazide on metabolic control in drug‐naïve patients with Type 2 diabetes mellitus. Methods A total of 1270 patients with Type 2 diabetes were randomized in a parallel‐group, double‐dummy, double‐blind study. Patients with poorly controlled Type 2 diabetes (HbA_1c 7.5–11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA_1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C‐peptide and pro‐insulin levels were measured. Results Mean HbA_1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: ?1.4%; gliclazide: ?1.4%; (90% CI: ?0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference ?0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: ?0.7 to ?0.1)]. Improvements in high‐density lipoprotein cholesterol (HDL‐C) and total cholesterol/HDL‐C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide. Conclusions Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA_1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.     

Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin‐ and sulphonylurea‐treated Type 2 diabetes

Aims Patients with diabetes rely on symptoms to identify hypoglycaemia. Previous data suggest patients with Type 2 diabetes develop greater symptomatic and hormonal responses to hypoglycaemia at higher glucose concentrations than non‐diabetic controls and these responses are lowered by insulin treatment. It is unclear if this is as a result of insulin therapy itself or improved glucose control. We compared physiological responses to hypoglycaemia in patients with Type 2 diabetes patients treated with sulphonylureas (SUs) or insulin (INS) with non‐diabetic controls (CON). Methods Stepped hyperinsulinaemic hypoglycaemic clamps were performed on 20 subjects with Type 2 diabetes, 10 SU‐treated and 10 treated with twice‐daily premixed insulin, and 10 age‐ and weight‐matched non‐diabetic controls. Diabetic subjects were matched for diabetes duration, glycated haemoglobin (HbA_1c) and hypoglycaemia experience. We measured symptoms, counterregulatory hormones and cognitive function at glucose plateaux of 5, 4, 3.5, 3 and 2.5 mmol/l. Results Symptomatic responses to hypoglycaemia occurred at higher blood glucose concentrations in SU‐treated than INS‐treated patients [3.5 (0.4) vs. 2.6 (0.5) mmol/l SU vs. INS; P = 0.001] or controls [SU vs. CON 3.5 (0.4) vs. 3.0 (0.6) mmol/l; P = 0.05]. They also had a greater increase in symptom scores at hypoglycaemia [13.6 (11.3) vs. 3.6 (6.1) vs. 5.1 (4.3) SU vs. INS vs. CON; P = 0.017]. There were no significant differences in counterregulatory hormone responses or impairment of cognitive function among groups. Conclusions Sulphonylurea‐treated subjects are more symptomatic of hypoglycaemia at a higher glucose level than insulin‐treated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals.     

Effects of patient‐tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low‐density lipoprotein cholesterol in patients with type 2 diabetes

Aims/Introduction

Recently, patient‐tailored statin therapy was proven effective for achieving target low‐density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type 2 diabetes.

Materials and Methods

The present study was an 8‐week, multicenter, single‐step titration trial of patient‐tailored atorvastatin therapy (10, 20 and 40 mg) according to baseline LDL cholesterol levels in 440 patients with type 2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high‐sensitivity C‐reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation.

Results

In the intention‐to‐treat analysis, 91% of the patients achieved their LDL cholesterol targets (<2.6 mmol/L) at week 8. There were significant reductions at week 8 in total cholesterol, triglycerides, non‐high‐density lipoprotein cholesterol (HDL) cholesterol, and the total cholesterol:HDL cholesterol ratio compared with the baseline values for all of the doses. The mean LDL particle size was significantly increased, and the small, dense LDL cholesterol levels were decreased in a dose‐dependent manner over the study period. In addition, the hsCRP levels were decreased in those high‐risk patients with baseline hsCRP levels over 3 mg/L (P < 0.001), and the adiponectin levels tended to increase with all of the doses (P = 0.004) at 8 weeks.

Conclusions

Patient‐tailored atorvastatin therapy based on LDL cholesterol at baseline was effective in ameliorating atherogenic LDL particle size and inflammation, in addition to achieving the target LDL cholesterol level without an undesirable effect on glycemic control in patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT01239849).     

[HDL‐C/apoA‐I]: A multivessel cardiometabolic risk marker in women with T2DM

Aims

Although women have higher high‐density lipoprotein cholesterol (HDL‐C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL‐C to its main apolipoprotein (apoA‐I) as [HDL‐C/apoA‐I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density.

Methods

We stratified 280 Caucasian T2DM women according to [HDL‐C/apoA‐I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β‐cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL‐C and apoA‐I: HDL size, HDL number, cholesterol load per particle (pP), apoA‐I pP, and HDL density.

Results

An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA‐I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β‐cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d^?1); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol^?1), associated with lower prevalence of microvascular/macrovascular complications: all‐cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all‐cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05).

Conclusion

[HDL‐C/apoA‐I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β‐cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women.     

Presence of very low density lipoprotein compositional abnormalities in Type 1 (insulin-dependent) diabetic patients; effects of blood glucose optimisation

Summary Plasma lipoprotein compositional abnormalities were investigated in eight normolipidaemic (plasma cholesterol <5.70 mmol/l; triglyceride <2.03 mmol/l) young male Type 1 (insulin-dependent) diabetic patients (before and after a short period of optimised blood glucose control) and in nine healthy control subjects, matched for sex, age and body mass index. Free and esterified cholesterol, triglyceride, phospholipids were assayed in all lipoprotein classes (VLDL, IDL, LDL) and in HDL subclasses (HDL2 and HDL3); apoB was measured only in very low density lipoproteins (VLDL). All VLDL constituents were increased in the diabetic group, the differences being more striking for apoB (6.0±1.1 mg/dl vs 2.0±0.1 mg/dl, p<0.02), free cholesterol (0.27±0.04 mmol/l vs 0.13±0.02 mmol/l, p<0.02) and esterified cholesterol (0.32±0.08 mmol/l vs 0.13±0.01 mmol/l, p<0.05). Also HDL subfractions showed differences between the two groups: all HDL2 constituents were increased, while in HDL3 only triglyceride was significantly increased (0.11±0.01 mmol/l vs 0.08±0.004 mmol/l, p<0.02). After two weeks of optimised blood glucose control all VLDL constituents were reduced and particularly: esterified cholesterol (–39%, p<0.02), free cholesterol (–37%, p<0.05), apoB (– 35%, p<0.05). Expressing each VLDL constituent as percent of the total lipoprotein mass, it was evident that the diabetic VLDL was rich in cholesterol both esterified (8.4±1.0% vs 5.4±0.5%, p<0.02) and free (8.5±0.7% vs 5.5±0.3%, p<0.001), apo B (5.1±0.6% vs 2.6±0.3%, p<0.001) and depleted in triglyceride (57.0±1.7% vs 64.1±1.7%, p<0.001). Two weeks of optimised blood glucose control were not able to correct the abnormal composition of VLDL. In conclusion, Type 1 (insulin-dependent) diabetic patients, although normolipidaemic, show an abnormal VLDL composition suggesting an increased prevalence of smaller and, possibly, more atherogenic VLDL particles. This abnormality is not corrected by a short period of blood glucose optimisation.     

Comparison of Bezafibrate and Simvastatin in the Treatment of Dyslipidaemia in Patients with NIDDM

Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia. However, these two groups of drugs have not been compared in diabetic patients in a randomized controlled trial. Therefore, a multicentre study was performed in 73 subjects with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and combined hyperlipidaemia (serum cholesterol 6.2–10.0 mmol l⁻¹, serum triglycerides 2.3–10.0 mmol l⁻¹), comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion. Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin (−41 % vs −22 %, p < 0.001) and increased HDL cholesterol more (bezafibrate: + 17 % vs simvastatin: + 9 %, p < 0.05). LDL cholesterol levels decreased by 14 % (p < 0.001) during simvastatin and increased by 21 % (p < 0.01) during bezafibrate. This increase in LDL cholesterol was positively correlated with fasting serum triglycerides (p < 0.001) and was associated with a reduction of the serum apolipoprotein B concentration, suggesting an increase in LDL particle size. Metabolic control of diabetes (fasting glycaemia; HbA_1c) and insulin secretion (C-peptide levels) were unaffected by both treatments. The incidence of side-effects during treatment was similar for both drugs. Thus, 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides. © 1997 John Wiley & Sons, Ltd.     

Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria

Summary The clinical importance of selection of different antihypertensive drugs for the treatment of diabetic patients is still unclear. Thus we performed a randomised, controlled study in 105 hypertensive non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria over 1 year. Patients received either the angiotensin converting enzyme (ACE) inhibitor ramipril (2.5–5.0 mg/day; in addition 24 % of patients also received felodipine) or the beta blocking agent atenolol (50–100 mg/day; in addition 24 % of patients also received hydrochlorothiazide). Blood pressure, metabolic control, lipid levels and albumin excretion rate were studied during the follow-up. After 1 year an almost identical fall (p < 0.001) in blood pressure was observed with ramipril (170/100 vs 150/85 mmHg, median) and atenolol (180/100 vs 150/80 mmHg, median). With ramipril a reduction of total cholesterol (6.3 vs 5.9 mmol/l), of LDL cholesterol (3.8 vs 3.6 mmol/l) and HDL cholesterol (1.3 vs 1.2 mmol/l) was found, whereas triglycerides slightly increased (1.8 vs 2.0 mmol/l). With atenolol a similar reduction of total cholesterol (6.3 vs 5.9 mmol/l), LDL cholesterol (3.8 vs 3.7 mmol/l) and HDL cholesterol (1.4 vs 1.2 mmol/l) and an increase of triglycerides (1.4 vs 1.7 mmol/l) was noted. Metabolic control of the patients was maintained with both ramipril and atenolol treatment. With ramipril treatment urinary albumin creatinine ratio (14.4 vs 13.8 mg/mmol) and creatinine clearance (82 vs 84 ml/min) were constant, but with atenolol an increase of albumin creatinine ratio (13.9 vs 19 mg/mmol, p < 0.001) and a slight decrease of creatinine clearance (80 vs 66 ml/min, p < 0.05, not significant after Bonferroni correction) was observed. In conclusion: 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar. Despite almost identical blood pressure reduction in both groups the albumin creatinine ratio was constant under ramipril, but increased under atenolol treatment. [Diabetologia (1996) 39: 1611–1616]     

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Aim To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose‐lowering drugs. Methods Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 ± 1 years) who were taking oral glucose‐lowering medication regularly were enrolled in this randomized, placebo‐controlled, double‐blind study. Changes in lipid profiles, oxidized low‐density lipoprotein (ox‐LDL), glycaemic control, components of the metabolic syndrome, C‐reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks. Results Low‐density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 ± 0.2 to 2.9 ± 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (–0.4 ± 0.1 vs. 0.2 ± 0.1 mmol/l, P < 0.001). Total cholesterol and total : high‐density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P < 0.001 and P = 0.032, respectively). However, ox‐LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups. Conclusions Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose‐lowering agents.     

Variability of lipids in patients with Type 2 diabetes taking statin treatment: implications for target setting

Aims To determine the biological variability of lipids in patients with Type 2 diabetes (T2DM) who are on statin treatment and then to assess any implications for current lipid targets. Methods A cross‐over study of biological variation of lipids in 26 patients with T2DM taking either simvastatin 40 mg or atorvastatin 10 mg. After 3 months on one statin, fasting lipids were measured on 10 occasions over a 5‐week period. Following 3 months on the other statin, 10 further samples were taken over 5 weeks. The main outcome measures were biological variability of total cholesterol (TC), low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol and triglycerides. Results The coefficient of variation (CV) of TC, LDL, HDL and triglycerides on simvastatin was 8.17, 13.11, 7.95 and 12.06%, respectively, whereas the CV on atorvastatin was 6.92, 10.30, 5.13 and 19.71%, respectively, with no statistically significant differences between statins. Treating to sustain a target TC < 5.0 mmol/l or LDL < 3.0 mmol/l means needing to maintain a mean TC of 4.3–4.4 mmol/l or LDL of 2.4–2.5 mmol/l. Treating to consistently achieve an LDL < 2.0 mmol/l means aiming for a mean of only 1.5–1.6 mmol/l. Conclusion In patients with T2DM taking either simvastatin or atorvastatin, the mean TC and LDL concentrations needed to consistently remain below a target are much lower than the target value itself. This means that guideline target limits extrapolated from the mean values of patients participating in clinical studies may overestimate the lipid reductions required.     

Efficacy and safety of alirocumab in insulin‐treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM‐INSULIN randomized trial

Aims

To investigate the efficacy and safety of alirocumab in participants with type 2 (T2D) or type 1 diabetes (T1D) treated with insulin who have elevated LDL cholesterol levels despite maximally tolerated statin therapy.

Methods

Participants at high cardiovascular risk with T2D (n = 441) or T1D (n = 76) and LDL cholesterol levels ≥1.8 mmol/L (≥70 mg/dL) were randomized 2:1 to alirocumab:placebo administered subcutaneously every 2 weeks, for 24 weeks' double‐blind treatment. Alirocumab‐treated participants received 75 mg every 2 weeks, with blinded dose increase to 150 mg every 2 weeks at week 12 if week 8 LDL cholesterol levels were ≥1.8 mmol/L. Primary endpoints were percentage change in calculated LDL cholesterol from baseline to week 24, and safety assessments.

Results

Alirocumab reduced LDL cholesterol from baseline to week 24 by a mean ± standard error of 49.0% ± 2.7% and 47.8% ± 6.5% vs placebo (both P < .0001) in participants with T2D and T1D, respectively. Significant reductions were observed in non‐HDL cholesterol (P < .0001), apolipoprotein B (P < .0001) and lipoprotein (a) (P ≤ .0039). At week 24, 76.4% and 70.2% of the alirocumab group achieved LDL cholesterol <1.8 mmol/L in the T2D and T1D populations (P < .0001), respectively. Glycated haemoglobin and fasting plasma glucose levels remained stable for the study duration. Treatment‐emergent adverse events were observed in 64.5% of alirocumab‐ vs 64.1% of placebo‐treated individuals (overall population).

Conclusions

Alirocumab produced significant LDL cholesterol reductions in participants with insulin‐treated diabetes regardless of diabetes type, and was generally well tolerated. Concomitant administration of alirocumab and insulin did not raise any safety concerns (NCT02585778).     

The prevalence of retinopathy in impaired glucose tolerance and recent‐onset diabetes in the Diabetes Prevention Program

Aims Retinopathy is considered the complication most closely associated with and characteristic of diabetes mellitus. Hyperglycaemia below levels diagnostic of diabetes, so called pre‐diabetes, is associated with a low prevalence of ‘diabetic’ retinopathy. However, few longitudinal studies of non‐diabetic populations have performed repeated measures of glycaemia and screened for retinopathy to determine its occurrence in the non‐diabetic population and the onset of retinopathy in new‐onset diabetic patients. We determined the prevalence of retinopathy characteristically seen in diabetes in persons with impaired glucose tolerance and in patients with new‐onset diabetes of known duration in the Diabetes Prevention Program (DPP) cohort. Methods The DPP recruited persons with elevated fasting glucose (5.3–6.9 mmol/l) and impaired glucose tolerance, and no history of diagnosed diabetes, other than gestational diabetes not persisting after pregnancy. Seven‐field, stereoscopic fundus photography was completed a mean of 3.1 years after the development of diabetes in 594 of 878 participants who had developed diabetes during the DPP, and in a random sample of 302 participants who remained non‐diabetic. Results Retinopathy consistent with diabetic retinopathy was detected in 12.6 and 7.9% of the diabetic and non‐diabetic participants, respectively (P = 0.03, comparing prevalence in the two groups). Systolic blood pressure and HbA_1c were higher at baseline in the diabetic participants who had retinopathy compared with the diabetic participants without retinopathy. Conclusions Retinopathy characteristic of diabetes is present in persons with elevated fasting glucose and impaired glucose tolerance and no known history of diabetes. The prevalence of retinopathy is significantly higher in persons who develop diabetes, even within 3 years of diagnosis.     

Efficacy and safety of sitagliptin monotherapy compared with voglibose in Japanese patients with type 2 diabetes: a randomized,double‐blind trial

Objective: To compare the efficacy and safety of sitagliptin (a dipeptidyl peptidase‐4 inhibitor) and voglibose (an α‐glucosidase inhibitor) monotherapy in Japanese patients with type 2 diabetes who have inadequate glycaemic control (HbA1c ≥6.5% and <10.0%) on diet and exercise. Methods: In a multi‐center, randomized, double‐blind, parallel‐group study, 319 patients were randomized (1:1) to 12‐week treatment with sitagliptin 50 mg once daily or voglibose 0.2 mg thrice daily before meals. The primary analysis assessed whether sitagliptin was non‐inferior to voglibose in lowering HbA1c. Results: After 12 weeks, sitagliptin was non‐inferior to voglibose for HbA1c‐lowering efficacy. Furthermore, sitagliptin was superior to voglibose, providing significantly greater reductions in HbA1c from baseline [least squares mean changes in HbA1c [95% confidence intervals (CI)] = ?0.7% (?0.8 to ?0.6) and ?0.3% (?0.4 to ?0.2), respectively; between‐group difference = ?0.4% (?0.5 to ?0.3), p < 0.001]. Sitagliptin was also superior to voglibose on other key efficacy endpoints, including change from baseline in 2‐h postmeal glucose (?2.8 mmol/l vs. ?1.8 mmol/l, p < 0.001) and fasting plasma glucose (?1.1 mmol/l vs. ?0.5 mmol/l, p < 0.001). After 12 weeks, the incidences of clinical adverse experiences (AEs), drug‐related AEs and gastrointestinal AEs in the sitagliptin group (48.5, 10.4 and 18.4%, respectively) were significantly (p < 0.05) lower than those in the voglibose group (64.7, 26.3 and 34.6%, respectively). The incidences of hypoglycaemia, serious AEs and discontinuations due to AEs were low and similar in both groups. Conclusions: In Japanese patients with type 2 diabetes, once‐daily sitagliptin monotherapy showed greater efficacy and better tolerability than thrice‐daily voglibose over 12 weeks.     

Relationship Between Inter‐Arm Difference in Systolic Blood Pressure and Arterial Stiffness in Community‐Dwelling Older Adults

A significant inter‐arm difference in systolic blood pressure (IADSBP) has recently been associated with worse cardiovascular outcomes. The authors hypothesized that part of this association is mediated by arterial stiffness, and examined the relationship between significant IADSBP and carotid‐femoral pulse wave velocity (CF‐PWV) in a sample from the Baltimore Longitudinal Study of Aging. Of 1045 participants, 50 (4.8%) had an IADSBP ≥10 mm Hg at baseline, and 629 had completed data from ≥2 visits (for a total of 1704 visits during 8 years). CF‐PWV was significantly higher in patients with an IADSBP ≥10 mm Hg (7.3±1.9 vs 8.2±2, P=.002). Compared with others, patients with IADSBP ≥10 mm Hg also had higher body mass index, waist circumference, and triglycerides; higher prevalence of diabetes; and lower high‐density lipoprotein (HDL) cholesterol (P<.001 for all). A significant association with IADSBP ≥10 mm Hg was observed for CF‐PWV in both cross‐sectional (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06–1.87; P=.01) and longitudinal (OR, 1.15; 95% CI, 1.03–1.29; P=.01) multivariate analyses. Female sex, Caucasian race, high body mass index (plus diabetes and low HDL cholesterol only cross‐sectionally) were other independent correlates of IADSBP ≥10 mm Hg. Significant IADSBP is associated with increased arterial stiffness in community‐dwelling older adults.     

Acute hyperglycaemia disturbs cardiac repolarization in Type 1 diabetes

Aims Patients with Type 1 diabetes have an increased risk of cardiovascular mortality. Notably, a prolonged heart rate adjusted QT interval (QTc) is a predictor of sudden cardiovascular death. Therefore, the objectives of this study were to investigate whether acute hyperglycaemia affects the QTc duration and the QTc dispersion in patients with Type 1 diabetes and in healthy volunteers. Methods Acute hyperglycaemia (15 mmol/l) for 120 min was induced in 35 males (22 men with Type 1 diabetes and 13 age‐matched non‐diabetic volunteers). All participants were non‐smokers without any diabetic complications. Electrocardiogram recordings were performed at normoglycaemia and at 0, 60 and 120 min of hyperglycaemia. Results Compared with normoglycaemia, acute hyperglycaemia increased the QTc interval in both patients with Type 1 diabetes (390 ± 6 vs. 415 ± 5 ms, P < 0.001) and in healthy volunteers (378 ± 5 vs. 412 ± 8 ms, P < 0.01). During hyperglycaemia, the QTc dispersion was prolonged in healthy volunteers (36 ± 4 ms vs. 54 ± 7 ms, P < 0.05) but not in patients with Type 1 diabetes (45 ± 3 ms at baseline vs. 48 ± 5 ms, NS). Conclusions Acute hyperglycaemia alters myocardial ventricular repolarization in patients with Type 1 diabetes and in healthy volunteers and might consequently be an additional risk factor for cardiovascular events.     

Ethnicity and glycaemic control are major determinants of diabetic dyslipidaemia in Malaysia.

AIMS: To define the prevalence of dyslipidaemia in young diabetic patients in Peninsular Malaysia and the contributory factors of dyslipidaemia in these subjects. METHODS: This is a cross-sectional study involving 848 young diabetic patients from seven different centres, with representation from the three main ethnic groups. Clinical history and physical examination was done and blood taken for HbA1c, fasting glucose, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides. RESULTS: The overall lipids were suboptimal, worse in Type 2 diabetes mellitus (DM) patients compared with Type 1 DM patients. Of the Type 2 patients, 73.2% had total cholesterol > 5.20 mmol/l, 90.9% had LDL-cholesterol > 2.60 mmol/l, 52.6% had HDL-cholesterol < 1.15 mmol/l and 27.3% had serum triglycerides > 2.30 mmol/l. There were ethnic differences in the lipid levels with the Malays having the highest total cholesterol (mean 6.19 mmol/l), and the highest LDL-cholesterol (mean 4.16 mmol/l), while the Chinese had the highest HDL-cholesterol (geometric mean 1.24 mmol/l). Ethnicity was an important determinant of total, LDL- and HDL-cholesterol in Type 2 DM, and LDL- and HDL-cholesterol and triglycerides in Type 1 DM. Glycaemic control was an important determinant of total, LDL-cholesterol and triglycerides in both Type 1 and Type 2 DM. Waist-hip ratio (WHR) was an important determinant of HDL-cholesterol and triglycerides in both types of DM. Gender was an important determinant of HDL-cholesterol in Type 2 DM, but not in Type 1 DM. Socioeconomic factors and diabetes care facilities did not have any effect on the dyslipidaemia. CONCLUSIONS: The prevalence of dyslipidaemia was high especially in Type 2 DM patients. Ethnicity, glycaemic control, WHR, and gender were important determinants of dyslipidaemia in young diabetic patients. Diabet. Med. 18, 501-508 (2001)     

Plasma High Density Lipoproteins and Lipolytic Enzyme Activities in Diabetic Patients

Eighty diabetic patients, consecutively selected from an out-patient clinic, were studied with regard to plasma lipoprotein levels, especially HDL. Patients treated with sulphonylureas had 24% lower HDL cholesterol concentrations (p<0.01) but only about 7% lower apo AI levels (n.s.) than those on insulin treatment. This difference could at least partly be explained by differences in age and type of diabetes. There was no relationship between the degree of diabetic control, as measured by fasting blood glucose levels, and HDL levels. In two subgroups of insulin-treated diabetics, selected to represent extremely low and high HDL levels (range 0.5–0.8 and 1.8–2.0 mmol/l, respectively) but matched with regard to age, duration of diabetes, insulin dosage and diabetic control, the activities of lipoprotein lipase and hepatic lipase in postheparin plasma were also recorded. The high HDL group had significantly higher lipoprotein lipase activities (p<0.01) and significantly lower hepatic lipase activities (p<0.05) than the low HDL group, supporting the hypothetical roles of these enzymes in HDL metabolism, and offering a tentative mechanism behind the large variability of HDL levels in diabetics.