bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Restriction Polymorphisms of the Apolipoprotein AI‐CIII‐AIV Gene Cluster: a Genetic Determinant of Atherosclerosis in Type 2 (Non‐insulin‐dependent) Diabetes Mellitus
Authors: Renard E. , Dupuy A. M. , Monnier L. , de Paulet A. Crastes
Published: July 2009

The presence of polymorphic restriction sites (S2, M2, P2) of the apolipoprotein AI‐CIII‐AIV gene cluster for the respective Sst1, Msp1, and Pst1 enzymes was assessed after hybridization with a radiolabelled apolipoprotein AI gene probe in 64 Type 2 diabetic patients and 67 healthy control subjects, all Europids. Twenty‐two diabetic patients showed evidence of ischaemic heart disease or macrovascular arteriopathy and forty‐two were free of cardiovascular complications. Control subjects were selected for the absence of personal or familial metabolic or cardiovascular diseases. The frequencies of polymorphic alleles were in agreement with previous studies in the control group: S2 6.3 (95% confidence interval (CI) 2.3–10.3)%, M2 5.5 (1.6–9.4)%, P2 6.3 (2.3–10.3)% and did not differ in the whole diabetic group: S2 4.2 (0.7–7.7)%, M2 6.5 (2.0–11.0)%, P2 6.6 (2.3–10.9)%. The relative prevalences of S2, M2, and P2 alleles were, respectively: 3.32, 1.54, and 2.00 (Woolf's ratio) in the macroangiopathic group but allele distribution frequencies were not statistically different from non‐macroangiopathic patients. The allelic associations S2M2P1 and S1M1P2 showed a relative prevalence of 2.86 and 2.00 in the presence of cardiovascular complications but the difference was not significant in terms of polyallelic distribution frequencies in the absence of atherosclerosis. No serum lipid abnormalities could be related to the presence of any polymorphic allele or allelic association. These results suggest a genetic influence on the development of atherosclerosis in Type 2 diabetes, but the mechanism remains unclear.
Metformin Causes a Reduction in Basal and Post‐venous Occlusion Plasminogen Activator Inhibitor‐1 in Type 2 Diabetic Patients
Authors: Grant P. J. , Stickland M. H. , Booth N. A. , Prentice C. R. M.
Published: July 2009

The effects of metformin on the fibrinolytic system were studied pre‐ and post‐venous occlusion in 38 Type 2 diabetic patients in a double‐blind, placebo‐controlled trial. After a 3‐week run‐in period, 21 patients received metformin and 17 placebo, for 6 weeks. In the metformin‐treated patients basal plasminogen activator inhibitor‐1 antigen (PAI‐1Ag) fell from 57.4 μg l−1 before treatment to 36.1 (p < 0.05) and 41.0 μg l−1 (p < 0.01) after 3 and 6 weeks therapy. In this group post‐venous occlusion PAI‐1Ag also fell after 3 weeks (p < 0.002) and 6 weeks (p < 0.05) treatment. There were no changes in either basal or post‐venous occlusion concentrations of PAI‐1Ag in the placebo treated group. The fall in PAI‐1Ag was not associated with an increase in basal plasminogen activator activity (PAA) which remained unchanged in both groups. Post‐venous occlusion values for PAA in the metformin treated patients were increased at 3 weeks (p < 0.05) although there was no difference at 6 weeks.
Neutrophil Aldose Reductase Activity and its Association with Established Diabetic Microvascular Complications
Authors: Dent M. T. , Tebbs S. E. , Gonzalez A. M. , Ward J. D. , Wilson R. M.
Published: July 2009

Direct investigation of the polyol pathway is rarely possible in studies of human diabetes. A spectrophotometric assay has been developed for the measurement of aldose reductase and sorbitol dehydrogenase activity in the neutrophil. Neutrophil aldose reductase activity was increased in patients with Type 1 diabetes with complications (median 40 (interquartile range 28–48) u, where 1 unit of enzyme activity = nmol NADPH min−1 108‐cells−1) compared with those without complications (20 (16–36) u, p < 0.01) and normal control subjects (20 (8–36) u, p < 0.01). In Type 2 diabetes, patients with complications also had higher aldose reductase activity (40 (28–52) u) than those without complications (24 (16–36) u, p < 0.01). There were no differences between patients without complications and normal control subjects. Sorbitol dehydrogenase activity was decreased in diabetic patients (p < 0.02) but not significantly different between diabetic patients with and without complications.
The Influence of Regional Adiposity on Atherogenic Risk Factors in Men and Women with Type 2 Diabetes
Authors: Baynes C. , Henderson A. D. , Anyaoku V. , Richmond W. , Johnston D. G. , Elkeles R. S.
Published: July 2009

To determine firstly whether body fat distribution could predict the presence of atherogenic risk factors better than overall adiposity in Type 2 diabetes, and secondly whether sex differences in these risk factors could be explained by sex differences in fat distribution, waist‐to‐hip girth ratio (WHR), serum lipids, lipoproteins, apolipoproteins, plasma lipolytic activity, and blood pressure were assessed in 47 patients with Type 2 diabetes, 21 women matched for age, body mass index (BMI) and blood glucose control with 26 men. The men had higher WHR (0.95 (range 0.83–1.07) vs 0.82 (0.74–0.94), p < 0.001), lower HDL‐cholesterol (1.03 ± 0.05 vs 1.38 ± 0.06 mmol l−1, p < 0.001) and apolipoprotein A1 (1.40 ± 0.06 vs 1.76 ± 0.06 gl−1, p < 0.001) concentrations, and higher hepatic lipase activities (16.2 (6.4–38.0) vs 8.6 (2.3–23.1) mmol h−1 l−1, p < 0.01). In both men and women, BMI and WHR were positively related to serum triglyceride, insulin and C‐peptide concentrations. In women, HDL‐cholesterol was negatively related to BMI (r = −0.45, p < 0.05) but only possibly related to WHR (r = −0.33, NS). In men, by contrast, WHR was related negatively to HDL‐cholesterol (r = −0.60, p < 0.005), HDL2‐cholesterol (r = −0.43, p < 0.05), and apolipoprotein A1 (r = −0.70, p < 0.001) and positively to hepatic lipase activity (r = 0.65, p < 0.001), whereas the same relationships with BMI were not significant. Neither WHR nor BMI was significantly related to systolic or diastolic blood pressure in men or women. When 10 men and 10 women were matched for WHR, the sex difference in HDL‐cholesterol, HDL2‐cholesterol and hepatic lipase activity lost statistical significance but apolipoprotein A1 and HDL3‐cholesterol remained significantly lower in men. WHR is thus a better predictor than BMI of several atherogenic risk factors in men (but not women) with Type 2 diabetes. The observed sex differences in factors relating to HDL metabolism can be only partially explained by differences in regional adiposity.
Human Insulin Use and Hypoglycaemia: Insights from the Pittsburgh Epidemiology of Diabetes Complications Study
Authors: Orchard T. J. , Maser R. E. , Becker D. J. , Dorman J. S. , Drash A. L.
Published: July 2009

Recently, concern has arisen that human (as opposed to beef or pork) insulin may cause more frequent and/or severe hypoglycaemia in association with reduced warning symptoms. This question was examined from questionnaire data of 628 Type 1 diabetic patients (mean age 28 years and duration of diabetes 19 years) participating in the baseline examination of a follow‐up study of diabetes complications. Those using human insulin (n = 73) reported an insignificantly higher frequency of hypoglycaemic reactions in the last year than those using animal insulin (66 vs 55 % with reactions at least monthly) and only a weak trend was seen overall for the prevalence of human insulin use to increase with increasing frequency of hypoglycaemia (p = 0.06). Hypoglycaemic reactions resulting in unconsciousness were too rare to permit analysis by type of insulin used. The prevalence of reduced awareness of hypoglycaemia was similar among human insulin users to that seen in animal insulin users (25 vs 19 %, NS). However, prevalence of reduced awareness showed a strong relationship to current blood glucose in the animal (r = −0.18, p<0.001) but not human (r = −0.06, NS) insulin users. Excluding patients with autonomic symptoms or neuropathy did not alter the results, nor did excluding the 34 individuals taking more than three insulin injections per day. It is concluded that human insulin use is not associated with either any substantial increased frequency of hypoglycaemia or reduction in awareness of hypoglycaemia. However, human insulin use does appear to be associated with reduced awareness of hypoglycaemia in those whose blood glucose control is relatively poor.
Are Conventional Risk Factors for Mortality Relevant in Type 2 Diabetes?
Authors: Fitzgerald A. P. , Jarrett R. J.
Published: July 2009

One‐hundred and ninety‐one men with Type 2 (non‐insulin‐dependent) diabetes mellitus, participants in the Whitehall Survey, were followed for 15 years. Age‐adjusted all‐cause and ischaemic heart disease (IHD) mortality rates were significantly increased in the diabetic men. Of four putative risk factors for IHD ascertained in the survey (plasma cholesterol, systolic blood pressure, cigarette smoking, body mass index) only blood pressure was a significant predictor in univariate Cox regression analysis. A review of comparable studies revealed lack of consistency in the association of these risk factors (derived from studies in non‐diabetic populations) and mortality in individuals with Type 2 diabetes. Given the absence of clinical trial data, risk factor intervention in Type 2 diabetes is currently based upon inference derived from studies in non‐diabetic subjects.
Renal Responses to Angiotensin II Infusion in Early Type 1 (Insulin‐dependent) Diabetes
Authors: Eadington D. W. , Swainson C. P. , Frier B. M. , Semple P. F.
Published: July 2009

The renal response to infusion of sub‐pressor doses of angiotensin II was examined in nine euglycaemic Type 1 (insulin‐dependent) diabetic patients with diabetes of short duration and nine non‐diabetic control subjects. Plasma concentrations of angiotensin II and of free insulin were similar in both groups at baseline and during angiotensin II infusion. Glomerular filtration rate (Inutest clearance) fell to a similar extent during angiotensin II infusion in both groups (diabetic 116(SE 5) to 102(5) ml min−1 1.73‐m−2; control 113(6) to 100(5) ml min−1 1.73‐m−2). There was a large dose‐dependent fall in effective renal plasma flow (p‐aminohippurate clearance) during angiotensin II infusion which was of similar magnitude in both groups (diabetic; 694(46) to 521(21) ml min−1 1.73‐m−2; control 665(41) to 498(30) ml min−1 1.73‐m−2). The absolute and the fractional rates of urinary excretion of sodium were both lower in the diabetic group throughout the study, but there was a comparable antinatriuretic response to angiotensin II. Thus, the renal haemodynamic response to angiotensin II infusion is normal in early well‐controlled Type 1 diabetes. Differences were found in the renal handling of sodium, which could not be related to altered renal tubular responses to angiotensin II or to peripheral hyperinsulinaemia.
Metabolic Control May Influence the Increased Superoxide Generation in Diabetic Serum
Authors: Ceriello A. , Giugliano D. , Quatraro A. , Russo P. Dello , Lefèbvre P.J.
Published: July 2009

Superoxide anion (O2‐) generation in serum from 10 Type 1 diabetic patients and 10 normal subjects was measured ex vivo. The amount of O2‐ production was significantly increased in diabetic serum 0.41 ± 0.04 (±SD) vs 0.14 ± 0.04 μmol l−1 min−1, p < 0.001) and correlated with fasting plasma glucose and glycosylated protein levels in both diabetic (r = 0.72, p < 0.01, and r = 0.62, p < 0.05) and normal (r = 0.75, p < 0.01 and r = 0.64, p < 0.05) subjects. Improved metabolic control in the diabetic patients was associated with a reduction of serum O2‐ production (0.28 ± 0.06 μmol l−1 min−1, p < 0.01), but the correlation between O2‐ levels and fasting plasma glucose and glycosylated protein concentrations was retained (r = 0.86 and r = 0.72, respectively, both p < 0.01).
Can General Practitioners Assess Diabetic Control? Can Anybody Do Any Better?
Authors: Bradshaw C. , Eccles M. P. , Choi H. Y.
Published: July 2009

A prospective study assessing the ability of various health professionals to estimate the control of diabetic patients from the accepted measures made for diabetes care was carried out. Patients were stratified into four categories according to the estimated HbA1c, and 45–60 % were accurately assigned by the professionals. Patients were also divided into two broader groups according to their need to have changes in treatment made. None of the professionals could assign patients with Type 1 diabetes into these two groups with an accuracy of >71%. With Type 2 diabetic patients accuracy improved up to 98% and there was little difference between the professionals. The current HbA1c was accurately predicted into two broad groups by the previous HbA1c alone in 89% of cases of Type 2 diabetes. These findings have implications for the routine care of diabetic patients and the education of health care professionals.
The Role of Insulin Insensitivity and Hepatic Lipase in the Dyslipidaemia of Type 2 Diabetes
Authors: Baynes C. , Henderson A.D. , Anyaoku V. , Richmond W. , Hughes C. L. , Johnston D. G. , Elkeles R. S.
Published: July 2009

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin‐mediated glucose disposal, basal and glucose‐stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL‐cholesterol (r=0.65, p<0.05), HDL2‐cholesterol (r=0.59, p<0.05), and apolipoprotein A1 (r=0.57, p<0.05) and negatively with apolipoprotein B (r=‐0.53, p<0.05) and total: HDL‐cholesterol ratio (r=‐0.68, p<0.01). Fasting C‐peptide correlated negatively with HDL‐cholesterol (r=‐0.76, p<0.01), HDL2‐cholesterol (r= −0.80, p<0.001) and apoprotein A1 (r=‐0.56, p<0.05) and positively with total:HDL‐cholesterol ratio (r=0.64, p<0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose‐stimulated plasma insulin and C‐peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL‐cholesterol independent of insulin insensitivity. In addition, fasting C‐peptide alone accounted for 70 % of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL‐cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.
Ambulatory Blood Pressure Measurement in Type 2 Diabetic Patients: Methodological Aspects
Authors: Hansen K. W. , Schmitz A. , Pedersen M. Mau
Published: July 2009

Ambulatory blood pressure was measured over 24 h on two occasions in 29 Type 2 diabetic patients age 65 (range 52–74) years, and the reproducibility compared with that of ordinary clinic measurements recorded by Hawskley's random zero sphygmomanometer. The variability of the difference between blood pressure measurements on the two occasions was twice as large for clinic measurement as for ambulatory measurement (2p < 0.01). If applied to clinical trials this would allow a fourfold reduction of patient numbers without losing test power. In the group of patients treated with antihypertensive medication (n = 16) the spontaneous decline in blood pressure after leaving the hospital proved to be most prominent in those patients with the highest clinic blood pressure, a phenomenon with importance for the management of hypertension. The individual difference between clinic measurements and ambulatory day‐time measurements from the same day was unpredictable. Ambulatory blood pressure measurement in the outpatient clinic may be a practicable approach for optimizing antihypertensive treatment in Type 2 diabetic patients.
Comparison of the Real‐time Use of Glycosylated Haemoglobin and Plasma Fructosamine in the Diabetic Clinic
Authors: Watts G. F. , Macleod A. F. , Benn J. J. , Slavin B. M. , Morris R. W. , Williams C. D. , Kearney E. M. , Lowy C. , Sönksen P. H.
Published: July 2009

The within‐clinic use of glycosylated haemoglobin (HbA1) and plasma fructosamine results in assessing blood glucose control and clinical management was compared in 1030 diabetic patients. The physician initially reviewed the patient with one randomly allocated measure (HbA1 or fructosamine) and completed a questionnaire concerning perception of blood glucose control, alteration to diet, alteration to medication, referral for diabetes education, and follow‐up interval. The patient was then re‐assessed using the second measure and the questionnaire repeated. Discordance rates for the study end‐points, judged as binary outcomes, were: blood glucose control 15 %; alteration to diet 7 %; alteration to medication 9 %; referral for education 3 %; follow‐up interval 4 %. A significantly greater number of patients were rated as poorly controlled with HbA1, than with fructosamine (p < 0.001) and were, in consequence, more frequently recommended alteration to diet and medication, referral for education and shorter follow‐up interval; the rate of discordance for at least one of the management decisions was 16%. Multifactorial analysis showed that discordant management was dependent on the reviewing physician (p < 0.001) and a history of cardiovascular disease (p < 0.01); but neither type of diabetes, nor presence of nephropathy or variant haemoglobins, nor plasma glucose concentration, significantly influenced the likelihood of a discordance. Replacing HbA1 with fructosamine in the diabetic clinic may result in significant differences in the physician's perception of blood glucose control and in the management of patients.
Impaired Microvascular Hyperaemic Response in Children with Diabetes Mellitus
Authors: Shore A.C. , Price K.J. , Sandeman D.D. , Green E.M. , Tripp J.H. , Tooke J.E.
Published: July 2009

Clinically detectable microvascular complications of diabetes are uncommon in children with diabetes especially in the prepubertal group. It is unclear whether subtle functional abnormalities of the microcirculation occur in children without evidence of clinical microangiopathy and in particular whether abnormalities can be demonstrated in children before puberty. The maximum hyperaemic response to direct local heating (44 °C) of the foot skin was measured by laser Doppler fluximetry in 50 diabetic and 50 non‐diabetic children. An impaired hyperaemic response occurred in the diabetic children compared with control children (diabetic 1.25 (95% CI 1.13‐1.37) V; control 1.74 (1.60‐1.88) V; p<0.001) and was significantly related to duration of diabetes but not to long‐term blood glucose control. The impaired response was also present in prepubertal diabetic children (diabetic 1.37 (1.16‐1.58) V; control 1.89 (1.67‐2.12) V; p<0.001). Systolic and diastolic blood pressure were significantly raised in the prepubertal diabetic children. These data suggest that a functional abnormality of the microcirculation occurs in children with diabetes in the absence of clinically detectable microangiopathy, and even before puberty.
Comparison of Indices of Islet B‐cell Function in Type 2 Diabetes in Relation to Insulin Effectiveness and Clinical Outcome
Authors: Coppack S.W. , Thursfield V. , Dhar H. , Hockaday T.D.R.
Published: July 2009

The most appropriate way to estimate islet B‐cell function in Type 2 diabetes is unclear, and this has led to many different techniques of measurement being used. We have examined the associations to two fasting and four glucose‐stimulated indices of islet B‐cell function in members of a group of 249 Type 2 patients, seeking correlations with concurrent glucose tolerance and antilipolytic effect, and with subsequent clinical outcome. The six B‐cell indices were interrelated to variable degrees (rs −0.21 to +0.92). Early glucose‐stimulated insulin output (incremental 1st‐phase insulin area) was not significantly positively correlated with the fasting plasma concentration of immunoreactive insulin at any time. Fasting immunoreactive insulin and ‘minimal model’ islet B‐cell parameters were poorly related to the rate constant for glucose clearance and the degree of antilipolysis (rs values between −0.13 and +0.40). Homeostatic model assessment of the fasting islet B‐cell function was more consistently related to these metabolic effects. Incremental first‐phase insulin area was the islet B‐cell index most consistently related to metabolic abnormalities (rs up to +0.56), and to subsequent need for oral hypoglycaemic or exogenous insulin therapy. No index of islet B‐cell function was consistently associated with the subsequent development of diabetic tissue damage.
A Relative Cost‐effectiveness Analysis of Different Methods of Screening for Diabetic Retinopathy
Authors: Sculpher M.J. , Buxton M.J. , Ferguson B.A. , Humphreys J.E. , Altman J.F.B. , Spiegelhalter D.J. , Kirby A.J. , Jacob J.S. , Bacon H. , Dudbridge S.B. , Stead J.W. , Feest T.G. , Cheng H. , Franklin S.L. , Courtney P. , Talbot J.F. , Ahmed R. , Dabbs T.R.
Published: July 2009

The relative cost and cost‐effectiveness of different methods of screening diabetic patients for sight‐threatening retinopathy are assessed. The resource costs per screening visit, both to the health service and to patients, of ophthalmoscopic examination by primary screeners including general practitioners, hospital physicians, and ophthalmic opticians are estimated together with those of a similar screening test by ophthalmological clinical assistants. The total resource cost per screen of screening using non‐mydriatic photography is also estimated. Using estimates of sensitivity, specificity, and prevalence generated in the screening of 3318 diabetic patients in three UK centres, the relative cost‐effectiveness of screening methods is estimated in terms of their cost per true positive case detected. On the assumption that a patient makes a special trip for eye screening, the cost per true positive case detected for primary screeners ranges from £633 for a GP‐screened group in one centre to £1079 for another GP‐screened group in a second centre; the cost per true positive case detected of photography ranges from £497 for a camera that is taken to general practices in one centre to £1546 for a hospital‐based camera. Relative cost‐effectiveness changes if, in some contexts, the screening can take place without requiring an additional patient visit, and is strongly related to the relative sensitivity of the screening methods and to the prior probability (prevalence or incidence) of retinopathy in the diabetic population.
Urinary Transferrin Excretion in Type 1 (Insulin‐dependent) Diabetes Mellitus
Authors: O'Donnell M.J. , Martin P. , Florkowski C.M. , Toop M.J. , Chapman C. , Holder R. , Barnett A.H.
Published: July 2009

Urinary excretion of transferrin and albumin was studied by radioimmunoassay in 47 adult patients with Type 1 diabetes and 28 control subjects. Median (range) urinary transferrin excretion rate was significantly elevated in the diabetic group 0.58 (0.02–2663.3) μg min−1 compared with the control group 0.04 (0.01‐0.28) μg min−1, p<0.001. Urinary transferrin:creatinine ratios (x 102) were different in diabetic 47 (0.6–958.0) μg mmol−1 and control groups 0.7 (0.06‐2.3) μg mmol−1, p<0.001. There were correlations between urinary transferrin and albumin excretion rates in diabetic (r=0.78, p<0.001) and control groups (r=0.81, p<0.05). Forty (85%) diabetic patients had elevated transferrin excretion rates, 18 (38.3%) had elevated albumin excretion rates. All diabetic patients with elevated albumin excretion rates had elevated transferrin excretion rates. Twenty‐one (77.8%) of the patients with normal albumin excretion rates had elevated transferrin excretion rates. Urinary excretion of N‐acetyl‐β‐d‐glucosaminidase was greater in diabetic patients than control subjects (142 vs 58 μmol h−1 I−1, p<0.001). There were correlations between transferrin and N‐acetyl‐β‐d‐glucosaminidase excretion (r=0.67, p<0.01) and albumin and N‐acetyl‐β‐d‐glucosaminidase excretion (r=0.63, p<0.01) in the diabetic group. Elevated urinary transferrin excretion rate may be a marker for renal dysfunction in diabetes mellitus.
Blood Rheology and Cardiovascular Risk Factors in Type 1 Diabetes: Relationship with Microalbuminuria
Authors: Jay R.H. , Jones S.L. , Hill C.E. , Richmond W. , Viberti G.C. , Rampling M.W. , Betteridge D.J.
Published: July 2009

Whole blood and plasma viscosity, erythrocyte aggregation and deformability, plasma fibrinogen, lipids, lipoproteins, apolipoproteins, and measures of blood glucose control were compared between 21 Type 1 diabetic patients with microalbuminuria (overnight albumin excretion rate 30–200 μg min−1) and 21 patients with albumin excretion below this range matched for age, sex, and duration of diabetes. Patients with microalbuminuria had significantly higher glycosylated haemoglobin (9.4±1.6 (±SD) vs 7.9±1.8% (normal range 5.0 to 7.6%)), total‐cholesterol (5.6±1.1 vs 4.6±1.3 mmol I−1), apolipoprotein B (0.82±0.21 vs 0.66±0.14 g I−1), and apolipoprotein B:A1 ratio (0.58±0.18 vs 0.50±0.15) than those without microalbuminuria (all p<0.05). HDL‐cholesterol was also raised (1.71±0.46 vs 1.43±0.37 mmol I−1, p<0.05). Lipoprotein(a) concentration was possibly higher in the microalbuminuric group (median (95% CI) 105 (82–140) vs 72 (52–114) mg I−1, p=0.06). No differences were seen in any of the rheological measurements. These results confirm the presence of potentially atherogenic lipoprotein changes in Type 1 diabetic patients with microalbuminuria, but suggest that altered blood rheology does not predate the development of nephropathy.
Central Rather than Generalized Obesity is Related to Hyperglycaemia in Asian Indian Subjects
Authors: Shelgikar K.M. , Yajnik C.S. , Hockaday T.D.R.
Published: July 2009

The relationship of body mass index and waist‐hip ratio with plasma glucose concentrations during an oral glucose tolerance test (OGTT) was studied in native Indian (Asian) subjects. A total of 389 subjects (131 non‐diabetic, 74 impaired glucose tolerant (IGT) and 184 Type 2 diabetic (newly diagnosed and untreated)) were studied. Prevalence of obesity (BMI 27.0 kg m−2 in men and 25.0 kg m−2 in women, 21% and 47%, respectively) was lower in people with Type 2 diabetes than that reported in white Caucasian and migrant Asian populations. Body mass index was highest in IGT subjects (26.1 (19.7−34.3) kg m−2, median (5‐95th centile)) and was higher in diabetic subjects (24.2 (19.3−32.2) kg m−2) than in non‐diabetic control subjects (23.5 (17.1−30.0) kg m−2). However, waist‐hip ratio was higher in both IGT (0.88 (0.75−0.98)) and diabetic subjects (0.88 (0.75−1.00)) than in non‐diabetic control subjects (0.83 (0.70−0.97)), with no difference between the hyperglycaemic groups. On multivariate analysis, fasting as well as 2‐h plasma glucose concentrations during OGTT were found to be related to waist‐hip ratio (p<0.01) and subscapular fat thickness (p<0.01) but not to body mass index (or triceps fat thickness). Thus, in native Indians central obesity seems to be a more important association of hyperglycaemia than generalized obesity.
Impaired Glucose Tolerance in Obesity is Associated with Insensitivity to Insulin in Multiple Aspects of Metabolism as Assessed by a Low Dose Incremental Insulin Infusion Technique
Authors: Robertson D.A. , Singh B.M. , Nattrass M.
Published: July 2009

To determine whether Impaired Glucose Tolerance gives rise to additional defects in insulin action in lipid and ketone metabolism, thirty‐two obese subjects were studied by low‐dose incremental insulin infusion. Sixteen had Impaired Glucose Tolerance and 16 had normal glucose tolerance. Body mass index was 36.9−80.9 kg m−2 and was similar in each group. In patients with Impaired Glucose Tolerance, plasma insulin was higher in the fasted state (logarithmic mean 14.5 (9.8−21.6) (−SD−+SD) vs 9.6 (6.4−14.5) mU I−1, p<0.01) and during the infusion (p<0.001). The metabolic clearance rate for insulin at the highest infusion rate was lower (14.2±0.8 (±SE) vs 18.9±2.1 ml kg−1 min−1, p<0.05) in these subjects. Basal hepatic glucose production was higher in subjects with Impaired Glucose Tolerance (6.3±0.4 vs 4.5±0.6 mol kg−1 min−1, p<0.02) and remained elevated during infusion (p<0.01). Glucose disposal per unit circulating insulin at the maximal infusion rate was approximately half in subjects with Impaired Glucose Tolerance (0.022±0.010 vs 0.047±0.017 ml kg−1 min−1 mU−1 I, p<0.01). When simultaneous insulin and metabolite concentrations during the infusion are plotted as dose‐response relationships, a difference in relative sensitivity to insulin in Impaired Glucose Tolerance over subjects with normal glucose tolerance is suggested for non‐esterified fatty acids 0.72 (95% CI 0.62−0.84) and glycerol 1.85 (1.37−2.49). These results suggest that Impaired Glucose Tolerance in obesity may be associated with reduced insulin clearance and additional insensitivity to insulin action in hepatic and peripheral glucose metabolism and fatty acid re‐esterification, but that this is not the case for lipolysis or ketogenesis.
Lipoprotein Lipids and Apolipoproteins (AI, AII, B, CII, CIII) in Type 1 and Type 2 Diabetes Mellitus in Young Kuwaiti Women
Authors: Al‐Muhtaseb N. , Al‐Yusef A.R. , Bajaj J.S.
Published: July 2009

Plasma lipid and apolipoprotein levels of Type 1 and Type 2 young Kuwaiti diabetic women on insulin therapy were investigated to elucidate the relationship between coronary artery disease risk factors and lipid levels. Forty Type 1 and 52 Type 2 diabetic women and 45 and 62 corresponding control subjects (matched for age and body mass index) were investigated. In comparison with control subjects, both groups of diabetic patients showed marked increases in total‐cholesterol, LDL‐cholesterol, triglycerides, very low density triglycerides, apolipoprotein B, glucose, fructosamine, and glycosylated haemoglobin HbA1c (all p < 0.001). However, apolipoprotein CIII was significantly elevated in Type 2 diabetic patients (p < 0.001) but not in Type 1 patients. Concentrations of apolipoproteins CII and All in both diabetic groups were not significantly different from those in control subjects. Levels of HDL–, HDL2− and HDL3−cholesterol and plasma apolipoprotein AI were markedly decreased in both the diabetic groups compared with their control groups (all p < 0.001 except HDL3−cholesterol in Type 1 diabetic vs control, p < 0.05). In Type 2 diabetic patients, HbA1c correlated positively with triglycerides (r = 0.70, p < 0.001), cholesterol (r = 0.60, p < 0.001), apolipoprotein B (r = 0.77, p < 0.001), and apolipoprotein CIII (r = 0.55, p < 0.001) and negatively with apolipoprotein AI (r = −0.49, p < 0.001). In Type 1 diabetic patients HbA1c correlated positively only with apolipoprotein CIII (r = 0.50, p < 0.001).
Impaired Glucose Tolerance and Diabetes Mellitus in Hindu Indian Immigrants in Dar es Salaam
Authors: Ramaiya K.L. , Swai A.B.M. , McLarty D.G. , Alberti K.G.M.M.
Published: July 2009

The prevalence of Impaired Glucose Tolerance (IGT) and diabetes mellitus was studied in a migrant Hindu Indian community in Dar es Salaam, Tanzania. Using 1985 WHO criteria, 75 g oral glucose tolerance tests (OGTT) were performed on 1147 (583 men; 564 women) subjects aged 15 years and over. The age‐standardized prevalence of IGT in men and women was 15.2 and 17.2%, and that of diabetes was 9.1% (6.5% known; 2.6% previously undiagnosed) and 9.0% (3.7% known; 5.3% previously undiagnosed), respectively. Diabetes was present in 12.9% of men and 12.8% of women aged 35 years and above. The overall age– and sex‐standardized prevalence of IGT was 16.2% and of diabetes 9.1%. The major risk factors associated with diabetes in both men and women were age, family history of diabetes, and physical inactivity, and in women body mass index (BMI). Age and BMI contributed to the higher frequency of IGT in women as compared with men while in men, age was the only contributory factor. Despite overweight and obesity being more frequent in women than men, age‐standardized prevalence rates of IGT and diabetes were similar between men and women. The decreased prevalence of diabetes in men and women performing moderate/heavy physical activity was independent of age and BMI.
Hypertriglyceridaemia and its Influence on Low Density Lipoprotein Regulation of Cellular Cholesterol Synthesis: a Comparison Between Hypertriglyceridaemic Diabetic and Non‐diabetic Patients
Authors: Owens D. , Stinson J. , Collins P. , Johnson A. , Tomkin G.H.
Published: July 2009

The present investigation was undertaken to examine the relationship between serum triglyceride and composition of lipoprotein. Six groups of patients were examined, three with Type 2 (non‐insulin–dependent) diabetes and three without diabetes. The groups were further categorized on the basis of their serum cholesterol and triglyceride levels into normocholesterolaemic (serum cholesterol < 6.5 mmol I−1) and hypercholesterolaemic (serum cholesterol > 6.5 mmol I−1) with and without hypertriglyceridaemia (serum triglyceride > or < 3.5 mmol ***l−1). Low density lipoprotein (LDL) composition was determined and regulation of cholesterol synthesis by LDL was assessed by measuring its effect on [14C]–acetate incorporation into mononuclear leucocyte cholesterol. LDL from the hypercholesterolaemic diabetic patients had a significantly higher esterified cholesterol content when the patients were normotriglyceridaemic (1.14 ± 0.04 vs 0.76 ± 0.04 g g−1; p < 0.01). The ability of LDL to suppress cholesterol synthesis (percent inhibition) was significantly less using LDL from the normocholesterolaemic diabetic patients or hypercholesterolaemic non‐diabetic or diabetic patients compared with LDL from the normocholesterolaemic non‐diabetic control subjects (47.4 ± 3.9%, 39.1 ± 5.1% and 35.2 ± 4.1% vs 59.5 ± 1.2%, p < 0.01). However, hypertriglyceridaemia had no effect on LDL suppression of cholesterol synthesis. We conclude that hypertriglyceridaemia alters LDL composition but the alteration is not associated with the ability of LDL to regulate cholesterol synthesis.
Basal and Stimulated Plasma Atrial Natriuretic Factor in Patients With Type 1 Diabetes With and Without Nephropathy
Authors: Mcknight J.A. , Roberts G. , Sheridan B. , Bell P.M. , Atkinson A.B.
Published: July 2009

Hypertension is linked to the development of nephropathy in Type 1 diabetes. Total exchangeable sodium is elevated in patients with Type 1 diabetes in good metabolic control, and correlates with blood pressure. Atrial natriuretic factor has been shown to have effects on sodium and blood pressure homeostasis in man. Basal and NaCl‐stimulated plasma atrial natriuretic factor was therefore studied in 33 patients with Type 1 diabetes. Seventeen had no evidence of nephropathy, 11 had incipient nephropathy (albumin excretion rate 20–199 μg min−1) and five had overt nephropathy. Seventeen age– and sex‐matched normal control subjects were also studied. Subjects fasted from 2200 h, rose at 0745 h and remained ambulant until 0945 h. After 15 min supine, 210.15 mmoll‐1 NaCl was infused over 4 h. Basal erect (0945 h.) plasma atrial natriuretic factor was 4.2 ± 0.5, 3.5 ± 0.4, 2.5 ± 0.2, and 2.5 ± 0.3 pmol l−1 in the control, non‐nephropathic, incipient‐nephropathic, and overt nephropathic diabetic groups, respectively (all NS). Levels in all groups increased in response to NaCI infusion, and the responses were not different between groups. Urinary sodium excretion for 12 h before NaCl infusion was not different between groups, but during the 12 h after the start of the infusion was significantly (p < 0.05) less in the Type 1 diabetic group without nephropathy than in the control group. These results suggest that atrial natriuretic factor does not play a major role in the development of changes in sodium balance which are associated with Type 1 diabetes and nephropathy.
A Community‐based Study of Diabetes‐related Skills and Knowledge in Elderly People with Insulin‐requiring Diabetes
Authors: Pegg A. , Fitzgerald F. , Wise D. , Singh B.M. , Wise P.H.
Published: July 2009

An open cross‐sectional study of elderly (age > 65 yr) patients with insulin‐requiring diabetes mellitus (n = 57) was undertaken to audit safety of self‐management. Levels of knowledge and management skills of hypoglycaemia, hyperglycaemia, and foot care were determined. The prevalence of hypoglycaemia, visual impairment, and at‐risk feet and the ability to perform practical procedures (insulin injection and self‐monitoring) were assessed. Drawing up insulin and self‐injection was correct in 84% and 76% of patients, but 53% of self‐monitored urine or blood tests were performed incorrectly. Twenty‐six per cent experienced hypoglycaemia at least monthly and 25% had been seen at the hospital with hypoglycaemia in the last year. Eighteen per cent did not know what action to take with hypoglycaemia. Forty‐six per cent did not know any hyperglycaemic symptoms or signs. Prompted with symptoms, 35% still did not know what to do and 21% would take inappropriate action when self‐monitored tests read high. Fifty‐one per cent had impaired vision, 61% peripheral neuropathy and 24% peripheral vascular disease, with the result that 78% had at‐risk feet. Fifteen percent inspected or washed their feet infrequently, 40% walked barefoot occasionally, and 47% would take potentially dangerous action in the event of foot injury. This study demonstrates serious deficiencies in the basic education and management skills in our elderly insulin‐requiring diabetic population that could result in morbidity and mortality. Greater effort and vigilance by health care professionals must be directed towards this group.
Accuracy, Patient Acceptance and Clinical Application of Capillary HbA1c Monitoring
Authors: Dunning P.L. , Weberruss M. , Ward G.M.
Published: July 2009

HbA1c values in capillary blood (50 μl) were compared with venous samples, assayed by HPLC (normal < 6.6%) in 64 Type 1 and Type 2 diabetic patients. One group (n = 43) collected capillary blood in the Outpatient Department simultaneously with a venous sample. The capillary sample collection was not supervised. A second group (n = 21) obtained two capillary samples during routine home blood glucose monitoring in Unistep containers within 2 days of the venous sample and posted them to the laboratory with a questionnaire about the ease of use and acceptance of the method. In the home collection group, 97% returned samples, there were no postal losses, and 75% returned questionnaires. Although 18% of patients had difficulty collecting the samples, all preferred the Unistep method to venepuncture. Correlation of capillary and venous samples was good for all patients (r = 0.97, n = 53). The mean absolute difference between the two methods was 0.36 ± 0.04 (± SE) %Hb. Eleven samples had to be excluded (insufficient blood; samples undated). The standard deviation for capillary duplicates was 0.14%, at a mean of 8.7%. During laboratory storage capillary HbA1c was initially slightly higher than corresponding venous values with some decrease (7.7% to 7.2%) over 7 days. HbA1c values in home‐collected samples are accurate and reproducible when compared with venous samples assayed by HPLC, and the method was acceptable to patients.
Changes in Brainstem Auditory Evoked Potentials During Insulin‐induced Hypoglycaemia in Type 1 Diabetic Patients
Authors: Ziegler D. , Hübinger A. , Gries F. A.
Published: July 2009

To determine whether the central and peripheral auditory pathways are disturbed during hypoglycaemia, brainstem auditory evoked potentials were measured in 16 Type 1 diabetic patients aged 17–55 years during intravenous insulin infusion. Within 60 min mean blood glucose declined from 5.0 mmol l‐1 to a nadir at 1.7 mmol l‐1 followed by an increase to 2.8 mmol l‐1 30 min after the insulin infusion had been discontinued. The latency of wave I of brainstem auditory evoked potentials remained unchanged during hypoglycaemia. However, latencies of waves III and V and interpeak latencies I–III, III–V, and I–V were significantly prolonged at average blood glucose levels of 1.7 or 2.1 mmol l‐1 when compared with baseline: III 3.96 ± 0.03 (±SE) vs 4.01 ± 0.04 ms; V 5.69 ± 0.07 vs 5.81 ± 0.07 ms; I–III 2.30 ± 0.05 vs 2.37 ± 0.05 ms; III–V 1.73 ± 0.06 vs 1.83 ± 0.07 ms; and I–V 4.01 ± 0.05 vs 4.14 ± 0.06 ms (all p < 0.05). When blood glucose was allowed to increase to 2.8 mmol l‐1, these conduction delays were no longer demonstrable. The depression of the brainstem was approximately paralleled by the activation of counter‐regulatory hormones and development of hypoglycaemic symptoms. We conclude that hypoglycaemia results in a rapidly reversible delay of the transmission time in the brainstem but not in the auditory nerve. The dysfunction in the brainstem suggests that not only cortical centres are involved in response to hypoglycaemia in Type 1 diabetic patients.
Minimal Models of Glucose Disappearance: Lessons from the Labelled IVGTT
Authors: Caumo A. , Giacca A. , Morgese M. , Pozza G. , Micossi P. , Cobelli C.
Published: July 2009

In this paper the domain of validity of the unlabelled and labelled minimal models of glucose disappearance is studied. Labelled intravenous glucose tolerance tests were performed in six normal subjects using 3‐3H‐glucose as the tracer. Insulin and unlabelled glucose data were analysed with the minimal model of glucose disappearance. The model provides estimates of glucose effectiveness (SG) and insulin sensitivity (SI) which measure the effects of glucose per se and insulin on both glucose production and disposal. Insulin and labelled glucose data were analysed with the labelled minimal model of tracer disappearance. Estimates of glucose effectiveness (SG*) and insulin sensitivity (SI*) which reflect disposal processes only were calculated. The results of the two minimal models suggest two areas of model error. Firstly, the relationships between labelled and unlabelled parameters contradict the theoretical expectation. Secondly, the time‐course of hepatic glucose production is unrealistic. Possible sources of these inconsistencies are an inadequate description of the glucose and/or insulin effect upon hepatic glucose production, and the assumption that glucose kinetics are monocompartmental. The monocompartmental description of glucose kinetics may affect both model parameters and hepatic glucose production and this leads to a critical reexamination of the previously published validation studies in which the minimal model metabolic indices have been compared with the analogous indices measured during glucose clamp studies.
Does Flexibility at Mealtimes Disturb Blood Glucose Control on a Multiple Insulin Injection Regimen?
Authors: Tunbridge F. K. E. , Home P. D. , Murphy M. , Alberti K. G. M. M.
Published: July 2009

Randomized crossover studies of a half‐sized lunch with reduced insulin dose in 21 patients, and a delayed (by 2 h) evening meal in 22 patients, compared with normal meals, were performed in Type 1 diabetic patients. The aim was to examine whether the size and timing of meals can be varied in patients on multiple injection regimens without disturbance of blood glucose control. All patients had previously had their control optimized on multiple injection therapy using a pen‐injector. The studies were carried out at home on 6 days (3 changed meals, 3 control) over 2 months, and as 8‐ and 7‐h metabolic profiles (1 study day, 1 control) in an investigation unit. A halved calorie lunch with half the usual insulin dose resulted in equivalent blood glucose control on the study day (area under curve: changed meal 40.0 ± 3.4 vs control meal 40.3 ± 3.5 mmol l‐1 h for the 5‐h period after the meal). Ketone body levels were also unchanged. The late evening meal shifted the post‐prandial blood glucose concentration accordingly, but the excursion was not different in extent from the control day (24.8 ± 1.9 vs 21.0 ± 1.7 mmol l‐1 h). A small excursion of 3‐hydroxybutyrate levels before the delayed meal (to 187 ± 48 μmol l‐1) was quickly corrected on eating. Hypoglycaemia was not different in frequency on the changed meal days. Thus no problems of clinical significance were observed when some flexibility in meal size and timing was allowed.
The Exeter Diabetic Project: An Acceptable District‐wide Education Programme for General Practitioners
Authors: Stead J. W. , Dudbridge S. B. , Hall M. S. , Gray D. J. Pereira
Published: July 2009

The Health District is a logical administrative unit for planning health services, and therefore the feasibility of delivering education for general practitioners across one such area was studied. By providing a suitable educational programme at convenient locations, it was possible to involve 89% out of 180 principals in General Practice in the Exeter Health District. Two‐thirds of these general practitioners attended educational sessions away from the District Postgraduate Centre. In a questionnaire answered by 81% of the involved general practitioners, 98% acknowledged responsibility for managing their diabetic patients, but 76% admitted to inadequate skills in retinal assessment. In a follow‐up postal questionnaire answered by 64% of general practitioners involved in the project, 74% found that they learnt from the retinopathy screening clinic and 100% found the sessions on eye disease helpful. The education programme was designed to link with a District‐wide retinopathy screening initiative.
Evaluative Procedures to Detect, Characterize, and Assess the Severity of Diabetic Neuropathy
Authors: Dyck P. J.
Published: July 2009

Minimal criteria for diabetic neuropathy need to be defined and universally applied. Standardized evaluative procedures need to be agreed and normal ranges determined from healthy volunteers. Types and stages of neuropathy should be established and assessments performed on representative populations of both Type 1 and Type 2 diabetic patients. Potential minimal criteria include absent ankle reflexes and vibratory sensation, and abnormalities of nerve conduction. However, the preferred criterion is the identification of more than two statistically defined abnormalities among symptoms and deficits, nerve conduction, quantitative sensory examination or quantitative autonomic examination. Various evaluative procedures are available. Symptoms should be assessed and scores can be assigned to neurological deficits. However, assessments of nerve conduction provide the most specific, objective, sensitive, and repeatable procedures, although these may be the least meaningful. Many techniques are available for quantitative sensory examination, but are poorly standardized and normal values are not available. For quantitative autonomic examination, tests are available for the adequacy of cardiovascular and peripheral vascular reflexes and increasingly for other autonomic functions. In any assessment of nerve function the conditions should be optimized and standardized, and stimuli defined. Specific instructions should be given and normal ranges established in healthy volunteers.