bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproducibility of the Short Insulin Tolerance Test
Authors: Hirst S. , Phillips D.I.W. , Vines S.K. , Clark P.M. , Hales C.N.
Published: July 2009

The short insulin tolerance test is a simple method of estimating insulin resistance by measuring the rate of fall of blood glucose following the intravenous administration of insulin. To determine its reproducibility, 18 healthy subjects underwent duplicate insulin tolerance tests separated by at least 1 week. Intravenous insulin (0.05 units kg−1) was administered into an antecubital vein and arterialized venous samples were obtained from a retrogradely cannulated vein on the dorsum of the hand on the same side. The test was terminated with an intravenous glucose injection 15 min after the administration of insulin. The mean whole blood glucose concentration fell from 4.6 mmol l−1 to 2.8 mmol l−1 while plasma insulin concentrations rose to supraphysiological levels and declined exponentially. The glucose disappearance rate (Kitt) calculated from the slope of the fall in log transformed blood glucose between 3 and 15 min after insulin injection ranged from 2.1 to 6.5 (mean 4.4) % min−1 during the first visit and 1.7 to 7.4 (mean 4.4) % min−1 during the second. The ratio of the within‐subject to between‐subject variance of the test was 0.24, the within‐subject coefficient of variation was 13 % and the between‐subject coefficient of variation 26 %. The short insulin tolerance test is reproducible and could be used to measure insulin resistance in large‐scale epidemiological studies.
Effect of Metabolic Control on Autonomic Function in Obese Patients with Newly Diagnosed Type 2 Diabetes
Authors: Vanninen E. , Uusitupa M. , Länsimies E. , Siitonen O. , Laitinen J.
Published: July 2009

To evaluate the effect of diet therapy and physical exercise on autonomic nervous function in newly diagnosed Type 2 diabetes, we followed 83 middle‐aged obese patients (48 men, 35 women) for a 15‐month period. After a 3‐month basic education programme the patients were randomized to one of two groups for comparison of standard treatment given by community health centres (conventionally treated group) and intensive dietary and exercise education (intervention group). Autonomic function was assessed by heart rate variability during deep breathing (expiration/inspiration ratio, E/I), and by systolic blood pressure response to standing up. The intensively treated women (n = 18) had the best blood glucose throughout the study, and this was the only group to show an improvement in E/I ratio (1.19 ± 0.03 vs 1.30 ± 0.05, mean ± SEM, p < 0.05). None of the groups showed any significant change in systolic blood pressure response to standing up. For further analyses, the original groups were combined and thereafter divided into those with declining fasting blood glucose during the intervention phase (n = 39) and into those with no change or increase in blood glucose level (n = 44). The group with improving blood glucose level showed an increase in E/I ratio (1.22 ± 0.02 vs 1.28 ± 0.03, p < 0.01) while in the other group E/I ratio remained unchanged (1.21 ± 0.02 vs 1.20 ± 0.02). The difference in E/I ratio between these two groups was significant at 15 months (p < 0.05). In conclusion, good blood glucose control is associated with an improvement in E/I ratio in patients with newly diagnosed Type 2 diabetes suggesting that cardiac autonomic dysfunction is at least in part functional in nature.
Are the Nutritional Recommendations for Insulin‐dependent Diabetic Patients Being Achieved?
Authors: Humphreys M. , Cronin C.C. , Barry D.G. , Ferriss J.B.
Published: July 2009

Dietary intake was assessed, using a 3‐day recorded food diary, in 122 patients with insulin‐dependent diabetes. Subjects were selected randomly from patients attending a diabetic clinic and stratified for age, sex, and duration of diabetes. The findings were compared to the dietary recommendations of the European Association for the Study of Diabetes (EASD) and to the findings in a recent Irish National Nutrition Survey. The average daily protein intake among diabetic patients was 18 % of the total calories, significantly higher than recommended by EASD and significantly higher than in the age‐matched general population. Dietary fat intake was on average 37 % of total calorie intake, again significantly higher than recommended and greater than in the general population among older patients. Saturated fat intake was higher than recommended and polyunsaturated fat intake was low. The average carbohydrate intake was 42 % of total calories, significantly lower than recommended and similar to that in the general population. Sugar intake was lower and starch intake was higher among patients than in the general population, however. Fibre intake was also lower than recommended, but was higher than in the general population. We conclude that the present dietary targets for diabetic patients are not being fully achieved.
Fluoxetine in the Treatment of Obese Type 2 Diabetic Patients
Authors: O'Kane M. , Wiles P.G. , Wales J.K.
Published: July 2009

In a 12‐month randomly allocated double‐blind trial in 19 obese Type 2 diabetic patients, fluoxetine 60 mg daily compared to placebo produced a significant fall in median body weight after 3 months (3.8 kg), 6 months (6.5 kg), 9 months (7.1 kg), and at 1 year (5.8 kg). Median fasting blood glucose and HbA1c levels fell significantly after 3 months (1.9 mmol l−1 and 1.7 %, respectively) and 6 months (1.8 mmol l−1 and 1.7%) but neither showed a significant difference to placebo after 9 or 12 months therapy with fluoxetine. There were no significant changes in serum cholesterol levels in the year but patients on fluoxetine showed a significant fall in serum triglyceride level (0.5 mmol l−1 after 3 months therapy but not thereafter. Compared to placebo there was a significant fall in median energy intake on fluoxetine after 3 months (257 kcal day−1) and 6 months (199 kcal day−1) but this difference was not significant at 9 or 12 months. There was also a significant fall in carbohydrate intake after 3 months (30 g day−1) and 6 months (23 g day−1) on fluoxetine as well as a significant fall in carbohydrate intake expressed as a percentage of the total daily energy intake; 5.9% at 3 months, 6.1% at 6 months, and 4.0% at 9 months. There were no significant effects on protein or fat intake except a significant increase in the intake of fat expressed as a percentage of daily energy intake, 5.9% after 6 months. Two of the nine patients on fluoxetine dropped out of the study due to gastrointestinal side‐effects. Fluoxetine might prove to be a useful adjunct therapy in obese Type 2 diabetic patients where short‐term weight loss and fall in carbohydrate intake and an improvement in glycaemia are indicated.
Increased Mortality Due to Cardiovascular Disease in Type 1 Diabetic Patients Transplanted for End‐stage Renal Failure
Authors: Kumar S. , Merchant M.R. , Dyer P. , Martin S. , Hutchison A.J. , Johnson R.W.G. , Boulton A.J.M. , Gokal R.
Published: July 2009

The graft and patient survivals following renal transplantation in all Type 1 diabetic patients transplanted within the North‐West of England between 1981 and 1990 at Manchester Royal Infirmary were studied. Fifty‐two Type 1 (insulin‐dependent) diabetic patients with end‐stage renal failure due to diabetic nephropathy were transplanted during this period. They were compared to controls matched for age, sex, and year of transplantation and also to all 904 patients transplanted during the same period. Graft survival rates at 1 and 5 years in the diabetic patients were lower (80.8% and 62.1%, respectively), compared to controls (88.9% and 77.9%, respectively, p = 0.02) but were similar to those seen in all grafts (80.4% and 59.0%, respectively, p = NS). Actuarial patient survival rate at 5 years was lower in diabetic patients (76.3%) compared to the control group (94.2%, p = 0.003). Myocardial infarction was the main cause (60%) of death in diabetic patients. The results of this large recent series indicate that good graft and patient survival rates can be obtained in Type 1 diabetic patients, although they remain poorer than those of patients with non‐diabetic renal disease. More rigorous pre‐transplantation cardiac assessment and treatment before acceptance of Type 1 diabetic patients for renal transplantation may help to improve patient survival.
A Four‐year Follow‐up Study on the Incidence of Diabetic Retinopathy in Older Onset Diabetes Mellitus
Authors: Agardh E. , Agardh C.‐D. , Koul S. , Torffvit O.
Published: July 2009

Out of 369 diabetic patients with an age at onset of diabetes ≧ 30 years previously studied, 325 (88%) were included in an ophthalmological follow‐up examination 4 years later. In patients treated with oral drugs at baseline, the incidence of any type of retinopathy was 30.8% and of severe retinopathy 5.7%. All patients who developed severe retinopathy received insulin during the follow‐up period. At baseline, duration of diabetes, diastolic blood pressure, and signs of nephropathy (p < 0.05 in all cases) as well as degree of metabolic control (p < 0.01) differed between patients who developed retinopathy and those who did not. At follow‐up, there were no longer any differences regarding degree of metabolic control and diastolic blood pressure. In patients treated with insulin at baseline, the incidence of any type of retinopathy was 41.0% and of severe retinopathy 16.1%. At baseline, duration of diabetes (p < 0.01), degree of metabolic control, and insulin dosage (p < 0.05 in both cases) differed between patients who developed retinopathy and those who did not. At follow‐up, there was no longer any difference in insulin dosage.
Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin Secretion
Authors: Phillips D.I.W. , Clark P.M. , Hales C.N. , Osmond C.
Published: July 2009

The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r=0.61, p < 0.001) but not insulin resistance (r= −0.05, p >0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = −0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA) also correlated well with insulin resistance (r= −0.57, p < 0.001) but not insulin secretion (r= 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance.
Evidence for Impaired Pancreatic Beta Cell Function in South African Indians with Impaired Glucose Tolerance
Authors: Motala A.A. , Omar M.A.K.
Published: July 2009

In a prospective study of South African Indians with impaired glucose tolerance (IGT), the serum insulin response during a 75 g oral glucose tolerance test (OGTT) was examined in 128 subjects who were classified as IGT 1 year previously (year 0) and in 60 matched control subjects. Based on the results at year 1, study subjects were divided into three groups, using World Health Organization criteria for glucose tolerance: IGT (n = 47), diabetes (n = 41), and transient IGT (normal glucose tolerance) (n = 40). When compared with the control group, despite higher plasma glucose concentrations, the IGT group showed similar fasting insulin, but lower 30‐min insulin response (57.4 ± 1.9 mUI−1 vs 86.5 ± 1.8, p<0.001) and lower 30‐min insulin/glucose ratio (7.4 ± 5.2 vs 13.3 ± 8.7, p < 0.001). The insulinogenic index was lower in the IGT group than in the control group at 30, 60, 90, and 120 min (p < 0.01, p < 0.001, p < 0.001, p < 0.001, respectively). The 2‐h insulin response was higher in the IGT group (106.7 ± 1.9 mUI−1 vs 59.2 ± 1.9, p < 0.01). The IGT group displayed a delayed pattern of insulin response with maximum levels only at 2‐h. Insulin area was similar in the two groups. In the transient IGT group, despite similar plasma glucose levels, the insulin responses at 0, 15, 30, and 60 min (p < 0.01, p < 0.001, p < 0.001, p < 0.001, respectively) were lower than in the control group; the 30‐min insulin/glucose ratio (7.1 ± 5.1 vs 13.3 ± 8.7, p < 0.001) and 60‐min insulinogenic index (46.9 ± 86.3 vs 123.4 ± 206.3, p < 0.001) were also lower in the transient IGT group. This study has shown that IGT in South African Indians is characterized by a diminished early phase insulin response and delayed (2‐h) hyperinsulinaemia during OGTT. Such findings would suggest that in this population group impaired early beta cell function is an important pathophysiological abnormality underlying IGT.
Severe Deterioration in Cognitive Function and Personality in Five Patients with Long‐standing Diabetes: A Complication of Diabetes or a Consequence of Treatment?
Authors: Gold A.E. , Deary I.J. , Jones R.W. , O'Hare J.P. , Reckless J.P.D. , Frier B.M.
Published: July 2009

Changes in mood, personality, and social function were examined in a group of five Type 1 diabetic patients, aged 50 to 66 years, with duration of diabetes from 24 to 47 years. Information on medical history was obtained from their carers and hospital records. All patients had experienced multiple episodes of severe hypoglycaemia and had impaired awareness of hypoglycaemia. Cerebral dysfunction predated the development of minimal diabetic complications and had been apparent for between 1 and 17 years. The carers assessed the pre‐morbid and present behaviour and personality of the patients using standard questionnaires. Significant deteriorations were demonstrated in cognitive (p = 0.04) and social functions (p = 0.04), compared with assessment of pre‐morbid function. Patients had tended to become more neurotic (p = 0.08) and less extravert (p = 0.07). All of the patients and three of the carers recorded scores suggestive of psychiatric morbidity on the General Health Questionnaire. The patients had experienced loss of employment and the carers described a reduction in the patients' social interactions. Although the aetiology of their cerebral dysfunction can not be definitely ascertained this case series emphasizes the need for long‐term prospective studies in patients with diabetes of long duration to assess the impact of the disorder on cognitive and social abilities particularly where there is evidence of cerebral dysfunction. The need for professional support for the carers of such patients should be recognized.
Comparison of Risk Factors for Foot Problems in Diabetic Patients Attending Teaching Hospital Outpatient Clinics in Four Different European States
Authors: Veves A. , Uccioli L. , Manes C. , Van Acker K. , Komninou H. , Philippides P. , Katsilambros N. , de Leeuw I. , Menzinger G. , Boulton A.J.M.
Published: July 2009

Although the St Vincent declaration calls for common European action in order to reduce major amputations, the differences in the incidence of foot problems and the prevalence of risk factors has not been fully investigated. We have examined the risk factors for foot ulceration and amputation in 278 consecutive patients (mean age 50.4 years, range 18–79 years) attending outpatient clinics of four teaching hospitals: Athens, Manchester, Rome, and Antwerp. There were no differences in age, weight or sex among the four groups but the percentage of patients with Type 1 diabetes was higher in Rome and Antwerp. Patients in Rome and Antwerp also had a longer duration of diabetes compared to Athens and Manchester. Mean vibration perception threshold was similar in all groups. No differences were found in the number of patients with moderate or severe clinical neuropathy (neuropathy disability score > 5), severe sensory loss (VPT > 25 V), and limited joint mobility. Symptomatic peripheral vascular disease was more frequent in Antwerp (p < 0.05) compared to the other three centres and foot ulceration in Rome compared to Manchester (p < 0.05). The number of smokers or ex‐smokers and the average alcohol consumption were similar in all centres. We conclude that, despite a few differences mainly in Type 1 diabetic patients, there are no major differences in the risk factors for foot ulceration and that, therefore, similar strategies for the prevention of foot problems may be equally successful in different European countries.
Ethnic Differences in Secretion, Sensitivity, and Hepatic Extraction of Insulin in Black and White Americans
Authors: Osei K. , Schuster D. P.
Published: July 2009

Hyperinsulinaemia and abnormalities in hepatic insulin extraction commonly coexist in ethnic groups with severe insulin resistance. Therefore, we compared the effects of ethnicity on glucose/insulin/C‐peptide dynamics, hepatic insulin extraction, and insulin sensitivity in healthy black (n = 32) and white (n = 30) Americans. Standard oral glucose tolerance test (OGTT) and tolbutamide‐modified, frequently sampled, intravenous glucose tolerance (FSIVGT) tests were performed in each subject. Insulin sensitivity index (S1) was calculated using the MINIMOD method described by Bergman et al. Basal and post‐stimulation hepatic insulin extraction were calculated by the molar ratios of C‐peptide and insulin concentrations during the basal steady state and areas under the post‐stimulation hormone curves, respectively. Apart from a slightly greater mean serum glucose peak response after oral glucose in the whites, mean glucose levels were identical in the blacks and whites during both stimulations. In contrast, serum insulin levels at basal and during both stimulations were significantly greater (2–3 fold) in the blacks than whites. However, the corresponding C‐peptide responses were identical in both groups. The basal and postprandial hepatic insulin extraction were 33% and 45% lower in the blacks when compared to whites, respectively. The mean S1 was significantly (p < 0.02) lower in the blacks (4.93 ± 0.46) than the whites (7.17 ± 0.88 × 10−4 (mU l−1)−1). We conclude that ethnicity may be a major determinant of the mechanism of peripheral hyperinsulinaemia and insulin insensitivity in black and white Americans.
The Value of the Neurometer in Assessing Diabetic Neuropathy by Measurement of the Current Perception Threshold
Authors: Pitei D.L. , Watkins P.J. , Stevens M.J. , Edmonds M.E.
Published: July 2009

The Neurometer is a relatively new device for assessing neuropathy by measuring current perception threshold (CPT). The study aim was to assess the ability of the Neurometer to distinguish between different types of nerve fibre damage by using different frequencies (2000 Hz, 250 Hz, and 5 Hz) of electric stimulus (high frequencies for large fibres and low frequencies for small fibres) and comparing the results with standard sensory tests of vibration perception threshold (VPT) and thermal perception threshold (TPT). CPT was determined on index finger and great toe of 51 patients with diabetic neuropathy and 28 non‐diabetic control subjects, age and sex matched. CPT in neuropathic patients could be distinguished from controls at all three frequencies in both feet and hands (p < 0.05). The best correlation was found between CPT at 2000 Hz and VPT (r = 0.48, p < 0.001) in the feet suggesting a degree of neuroselectivity. Internal correlations between CPT at the three frequencies showed the weakest correlation between CPT at 2000 Hz and 5 Hz (r = 0.27, p < 0.005), suggesting also that possibly different types of fibres were examined. CPT reproducibility was better in control (CV = 6.4–27.7%), than in neuropathic subjects (CV = 28.4–52.3%), although the coefficient of variation was comparable to that of standard tests of sensory function, VPT and TPT. The Neurometer is a simple instrument to use in clinical practice. It has a degree of neuroselectivity but like all subjective sensory tests has a large variability.
Elevated Vibration Perception Threshold in Young Patients with Type 1 Diabetes in Comparison to Non‐diabetic Children and Adolescents
Authors: Olsen B.S. , Nir M. , Kjær I. , Vølund A. , Mortensen H.B.
Published: July 2009

The vibration perception threshold (VPT) was investigated by biothesiometry in 61 children (28 boys) with Type 1 diabetes, mean age 15.5 (range 10–21) years, duration of diabetes 6.9 (range 1–19) years, and in 76 healthy children (39 males), mean age 13.8 (range 10–19) years. The measurements were performed in triplicate on the right second finger and on the right first toe. The vibration perception threshold was significantly increased (p < 0.0001) in the young diabetic patients (mean ± SD, finger 4.1 ± 1.1 V, toe: 5.7 ± 1.3 V) compared to healthy children (finger 3.4 ± 0.9 V, toe: 3.6 ± 1.3 V). Twenty percent of adolescents with Type 1 diabetes had a VPT above the 95th percentiles (finger: 5 V, toe 6.5 V) for normal control children. In healthy controls a significant correlation (r = 0.27, p < 0.01) was found for VPT in finger versus toe. This relationship was not significant in the diabetic group and may be due to reduced sensitivity of the fingertips caused by frequent blood glucose testing. Age, Tanner stage and height were significantly correlated to VPT (toe) in both diabetic and normal boys, while duration of diabetes, HbA1c, arterial blood‐pressure and body mass index were not significantly associated with VPT in any of the groups. The results indicate that changes in VPT appears early in childhood and emphasize a need for further studies of subclinical neuropathy in young patients with Type 1 diabetes.
Low Plasma Ascorbate Levels in Patients with Type 2 Diabetes Mellitus Consuming Adequate Dietary Vitamin C
Authors: Sinclair A.J. , Taylor P.B. , Lunec J. , Girling A.J. , Barnett A.H.
Published: July 2009

Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4‐day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 ± 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 ± 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 ± 28.3 (patients) vs 69.5 ± 33.4 (controls) mg; questionnaire, 54.0 ± 28.9 (patients) vs 65.0 ± 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 ± 19.1 μol l−1) and dehydroascorbate (27.6 ± 6.4 μmol l−1) levels were significantly lower in patients vs in controls (68.8 ± 36.0 and 31.8 ± 4.8 μmol l−1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake. Vitamin C supplementation of the diabetic diet deserves further consideration.
The Effect of Diabetes and Impaired Glucose Tolerance on Mortality in Malta
Authors: Tuomilehto J. , Schranz A. , Aldana D. , Pitkäniemi J.
Published: July 2009

A random sample of the middle‐aged population of Malta was studied in a diabetic survey in 1981. Among the 1537 survey responders, in 659 men and 878 women aged 40 years or more the prevalence of diabetes was 16 % in men and 18 % in women, and that of IGT 5 % in both sexes. By the end of 1985, 90 subjects (49 men: 41 women) had died. Mortality/1000 (95 % CI) was among subjects with normal, impaired glucose tolerance and diabetes in the age group 40–59 years 12 (5–19), 25 (23–73), and 61 (17–148), and in the age group of more than 60 years, 102 (68–136), 148 (59–237), and 178 (122–234), respectively. Age standardized mortality/1000 was in men 51, 28, and 100, and in women 34, 33, and 72 in the three categories of glucose tolerance, respectively. Among diabetic subjects aged 40–64 years the risk of death was increased seven‐fold as compared with normoglycaemic subjects. Among men there was an inverse association between body mass index and mortality in all categories of glucose tolerance. Among women, no clear trend between body mass index and mortality was found. The relative risk of death for subjects with diabetes adjusting for age, sex, and body mass index was 2.2 (odds ratio: 95 % CI 1.40 to 3.42) as compared with non‐diabetic subjects. The age‐adjusted survival curves for normoglycaemic subjects were similar for men and women. Among subjects with abnormal glucose tolerance the survival was slightly better in women than in men (p = 0.056). About half of the deaths were from cardiovascular disease and 7 % from diabetes mellitus.
Growth During Childhood and Final Height in Type 1 Diabetes
Authors: Brown M. , Ahmed M.L. , Clayton K.L. , Dunger D.B.
Published: July 2009

The growth of 184 children with Type 1 diabetes was analysed using data collected prospectively in the Oxford district between 1969 and 1992. The overall mean height standard deviation score (Ht SDS ± SD) at diagnosis was 0.35 ± 1.05 which was significantly greater than the national standard of Tanner (1966). However, there is evidence of a secular trend in the heights of Oxford children over the last 20 years when compared with Tanner. When data from children with diabetes were compared with local controls, it was only the children aged 5–10 years at diagnosis who were taller (Ht SDS ± SD, 0.58 ± 1.14, versus 0.31 ± 0.90, n = 73, p ± 0.05). Those diagnosed under the age of 5 years (n = 37) were shorter (Ht SDS 0.12 ± 0.93) and those diagnosed aged more than 10 years (n = 74) were similar in size (Ht SDS 0.22 ± 0.98) to controls. These differences could not be explained by social class. Loss of height occurred between diagnosis and puberty, particularly in those diagnosed between the ages of 5 and 10 years. The pubertal growth spurt was blunted in all groups but this abnormality was more profound in the girls (mean peak height velocity SDS ‐1.09 ± 1.02, p ± 0.0005) than in the boys (mean peak height velocity SDS ‐0.5 ± 1.14, p ± 0.025). The mean final height SDS was ‐0.74 ± 0.96 in those diagnosed < 5 years, 0.00 ± 1.26 in those diagnosed between the ages of 5 and 10 years and 0.09 ± 1.10 in those aged more than 10 years at diagnosis. Overall final heights were not significantly different from the mid‐parental height SDS. It is of interest that those children who were diagnosed under 5 years had short parents (mid‐parental height SDS, ‐0.39 ± 1.09). Height at diagnosis may reflect the heterogeneity of genetic and environment factors in the aetiology of diabetes. Growth following diagnosis is abnormal although there is no major impact on final height.
Mutations in the Glucokinase Gene are not a Major Cause of Late‐onset Type 2 (Non‐insulin‐dependent) Diabetes Mellitus in Japanese subjects
Authors: Nishi S. , Hinata S. , Matsukage T. , Takeda J. , Ichiyama A. , Bell G.I. , Yoshimi T.
Published: July 2009

The role of the glucokinase gene in the development of diabetes in a group of 349 Japanese subjects with late‐onset Type 2 diabetes was examined. These diabetic subjects and 197 non‐diabetic controls were typed at two simple tandem repeat DNA polymorphisms in the glucokinase gene termed GCK2 and GCK3. Six and five alleles were evident in Japanese subjects at GCK2 and GCK3, respectively. There were no significant differences in allele, genotype or haplotype frequencies between diabetic and normal groups. In addition, the glucokinase gene of 340 diabetic and 170 non‐diabetic Japanese subjects was screened for mutations using single strand conformation polymorphism analysis. Four nucleotide substitutions were identified: a silent substitution in exon 4 in the codon for proline 145 (CCC→CCG), and A→T, C→G, and C→A substitutions in introns 1b, 3, and 5, respectively. There were no significant differences in the frequencies of these nucleotide substitutions between diabetic and non‐diabetic groups. These results suggest that glucokinase gene defects are not a major cause of late‐onset Type 2 diabetes in Japanese subjects.
Do Doctors Address the Concerns of Patients with Diabetes?
Authors: Benett I. J.
Published: July 2009

Diabetes has an impact on people at both a biomedical and a holistic level. Furthermore there is a legitimate and substantial ‘medical agenda’ which doctors must address. But does this mean that they fail to deal with the concerns of their patients? A questionnaire study of diabetic patients attending the Manchester Diabetes Centre found that not all the patients' concerns were addressed in 25.5% of consultations. 220 (98%) patients were recruited from 225 approached. Not surprisingly, those who expressed three or more concerns were significantly less likely to have all their concerns addressed compared with those who had only one or two concerns (p = 0.001). The probability of having an individual concern addressed was 0.82. It was also found that Black‐Caribbeans were significantly less likely to have their concerns addressed than Whites especially if they were over 60 years old (p = 0.03). This study concludes that doctors should be particularly aware of the needs of patients who express many concerns, and especially if they are Black‐Caribbeans. Further research should develop strategies for improving the ability of doctors to identify and address the concerns of their patients.
The Effect of Recombinant Insulin‐like Growth Factor I on Ketone Body, Lipid and Apolipoprotein Concentrations and its use to Treat Ketoacidosis in Severe Insulin Resistance
Authors: Quin J. D. , Smith K. , Beastall G. H. , Miell J. P. , MacCuish A. C.
Published: July 2009

The effect of recombinant insulin‐like growth factor I (rhlGF‐I) on ketone body concentrations was studied in a patient with the Mendenhall syndrome, a rare insulin‐resistant state. Treatment with intravenous rhlGF‐I for an episode of ketoacidosis led to a clinical and biochemical improvement. One month later, the effect of 20 mg rhlGF‐I infused daily for 4 days on ketone body concentrations was studied. From peak concentrations 24 h prior to the study to a nadir 72 h after the infusion commenced, acetoacetate fell from 4.17 mmol l‐1 to 0.86 mmol l‐1, β‐hydroxybutyrate from 9.91 mmol l‐1 to 2.03 mmol l‐1, and acetone from 2 mmol l‐1 to 0.4 mmol l‐1. Further studies of rhlGF‐1 use caused a fall in concentrations of cholesterol, triglyceride, VLDL, LDL, and apolipoprotein B. Infusion of rhlGF‐1 reduces ketone body concentrations and may be life‐saving in the treatment of ketoacidosis developing in a patient with a severe insulin‐resistant state.
Effects of Heparin‐induced Non‐esterified Free Fatty Acid on Minimal Model‐derived Insulin Sensitivity in Individuals with Varying Degrees of Glucose Intolerance
Authors: Osei K. , Schuster D.P.
Published: July 2009

The effects of heparin‐induced non‐esterified free fatty acid (NEFA) release on insulin sensitivity index were studied in individuals with varying degrees of glucose intolerance and beta cell dysfunction during the frequently sampled intravenous glucose tolerance test (IVGTT). The groups comprised: Group 1 (n = 5): newly diagnosed Type 2 diabetic patients, Group 2 (n = 11): impaired glucose tolerance patients (IGT), and Group 3 (n = 16): healthy normal glucose tolerance subjects. The serum insulin and c‐peptide levels were severely blunted in the diabetic patients when compared to both non‐diabetic groups. Mean fasting and post‐heparin plasma NEFA levels were approximately 1.8 fold greater (p < 0.05) in the diabetic patients when compared to the other two groups. The mean insulin sensitivity index was lowest in the diabetic patients, intermediate in the IGT patients, and highest in the healthy controls. A significant negative relationship was found between the insulin sensitivity index and stimulated NEFA (r = −0.537, p < 0.008) but not with the fasting NEFA levels in our subjects. In summary, the frequently sampled IVGTT protocol that employs heparin flushes results in marked elevations in NEFA in Type 2 diabetic patients with poor beta cell dysfunction but not in subjects with intermediate or normal glucose tolerance. The higher plasma NEFA levels during heparin injections could worsen the model‐derived, insulin sensitivity index and could impair the ability to achieve an acceptable modelling in Type 2 diabetic patients. We therefore suggest heparin should be avoided in such patients when using this protocol.
Neutrophil Bactericidal Function in Diabetes Mellitus: Evidence for Association with Blood Glucose Control
Authors: Gallacher S.J. , Thomson G. , Fraser W.D. , Fisher B.M. , Gemmell C.G. , MacCuish A.C.
Published: July 2009

Neutrophil bactericidal activity was assessed in patients with type 1 (n=45) and Type 2 diabetes mellitus (n=68) and non‐diabetic control subjects (n=40) by measurement of whole blood chemiluminescence. Though chemiluminescence values tended to be highest in the non‐diabetic subjects these differences were not statistically significant (mean ± SD) (2.73 ± 1.65 mV (controls), 2.33 ± 1.41 mV (Type 1 diabetes) and 2.38 ± 1.12 mV (Type 2 diabetes), F=1.12, p=0.33). Significant negative correlations were evident, however, in patients with both Type 1 and Type 2 diabetes between chemiluminescence and glycated haemoglobin (rs=‐0.35, p=0.005 (Type 1), rs=‐0.45, p=0.002 (Type 2), fructosamine (rs=‐0.36, p=0.003 (Type 1), rs=‐0.42, p=0.004 (Type 2)), and random blood glucose (rs=‐0.25, p=0.04 (Type 1), rs=‐0.48, p=0.001 (Type 2)). Changes in whole blood chemiluminescence in a further group of 10 patients with Type 2 diabetes mellitus commenced on insulin therapy were followed for 21 days. Serum fructosamine concentrations fell significantly over this time (524 ± 58 μmol l−1 to 405 ± 47 μmol l−1, p<0.001), however, although chemiluminescence values tended to rise these changes were not statistically significant (1.01 ± 0.38 mV to 1.60 ± 0.91 mV, S=4.24, df=5, p=0.52). These results suggest that impaired neutrophil bactericidal function is associated with poor blood glucose control. While it is likely that neutrophil bactericidal function will improve as blood glucose control improves, further studies are required both to confirm this and to demonstrate a reduction in the incidence of clinical bacterial infection.
Diabetes in the Elderly
Authors: Meneilly G.S. , Tessier D.
Published: July 2009

Diabetes affects at least 20% of the population over the age of 65. Half of these patients are unaware that they have the disease. Diabetes in middle‐aged subjects is characterized by an impairment in glucose induced insulin release, increased fasting hepatic glucose output and resistance to insulin mediated glucose disposal. In contrast, diabetes in the elderly is primarily associated with insulin deficiency. The presentation of diabetes in the aged is often non‐specific. The elderly have an increased frequency of complications from diabetes. They are particularly susceptible to hypoglycaemia, because of reduced awareness of hypoglycaemic warning symptoms and altered release of counterregulatory hormones. Although no data are yet available from randomized controlled trials, there is abundant epidemiological evidence to suggest that adequate control of blood glucose can be expected to reduce the risk of long‐term complications. A team approach is ideal for the management of the elderly patient with diabetes. Little data is available on which to base a diet and exercise prescription for elderly patients. Gliclazide appears to be the sulphonylurea of choice in the aged because it is associated with a lower frequency of hypoglycaemic reactions. Urine glucose testing is unreliable, and capillary glucose monitoring is preferred. Fructosamine may prove to be superior to haemoglobin A1c for monitoring long‐term control.
The Effect of the Timing and the Administration of Acarbose on Postprandial Hyperglycaemia
Authors: Rosak C. , Nitzsche G. , König P. , Hofmann U.
Published: July 2009

To clarify the optimum timing for ingestion of acarbose, a 100 mg dose of this oral hypoglycaemic agent was administered 30 min before, at the beginning, and 15 min after ingestion of a test meal, and the effects of the drug on blood glucose rises were compared with increases observed after a control meal (no drug). Twenty‐four patients with Type 2 diabetes were included in a randomized, open, cross‐over study. The smallest increases in blood glucose (p < 0.001) occurred when acarbose was taken at the beginning and 15 min after starting the test meal (3.3 ± 1.6 mmol I−1 and 3.3 ± 1.4 mmol I−1). The increase in blood glucose levels when acarbose was taken 30 min before the test meal was significantly higher (4.2 ± 1.8 mmol I−1) and it was at its maximum following the control meal (5.2 ± 1.7 mmol I−1). Similar results were observed when the effects of acarbose on insulin and C‐peptide levels were measured. It is recommended that patients should be instructed to take acarbose with their first mouthful of food.
Angiotensin Converting Enzyme (ACE) Insertion/Deletion (I/D) Polymorphism, and Diabetic Retinopathy in Subjects with IDDM and NIDDM
Authors: Nagi D.K. , Mansfield M.W. , Stickland M.H. , Grant P.J.
Published: July 2009

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 ± 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 ± 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non‐proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p <0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of ***I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE ***I/D genotype was similar in subjects with IDDM, NIDDM, and controls (χ2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (χ2 = 3.42, df = 2, p = ns) or NIDDM (χ2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (χ2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.
Microvascular Function in Type 2 (Non‐insulin‐dependent) Diabetes: Improved Vasodilation After One Year of Good Glycaemic Control
Authors: Jaap A. J. , Pym C. A. , Seamark C. , Shore A. C. , Tooke J. E.
Published: July 2009

Abnormalities of microvascular function may be important in the development of diabetic microangiopathy. The major functional abnormality identified in patients with Type 2 diabetes has been a marked limitation of microvascular vasodilation, which is present from the time of diagnosis. The effects of sustained improvements in glycaemic control on vasodilator capacity in Type 2 diabetes are unknown. Twelve Type 2 diabetic patients were studied prospectively for 1 year after diagnosis. The reduced maximum hyperaemic response to local heating of the foot skin present at the time of diagnosis remained unchanged after 3 months of improved glycaemic control (1.12 ± 0.56 V at diagnosis vs 1.21 ± 0.69 V at 3 months, mean ± SD; p = 0.25), but was improved after 1 year (1.42 ± 0.91 V; p = 0.04 vs 3 months). The percentage increase in maximum hyperaemia correlated with the percentage decrease in HbA1c (rs = 0.53, p = 0.04). These results suggest that the early microvascular abnormalities demonstrated in Type 2 diabetes are potentially reversible and provide a further reason for striving for optimal glycaemic control in this patient group.
The Urinary Concentration of Sialic Acid is Increased in Non‐insulin‐dependent Diabetic Patients with Microangiopathy: a Possible Useful Marker for Diabetic Microangiopathy
Authors: Suzuki K. , Ishida H. , Sugimoto C. , Taguchi Y. , Matsuda H. , Nosaka K. , Someya Y. , Kadowaki S. , Seino Y.
Published: July 2009

In order to investigate the relationship between urinary excretion of sialic acid and the severity of diabetic microangiopathy, urinary levels of sialic acid were determined in patients with non‐insulin‐dependent diabetes mellitus. The urinary molar ratio of sialic acid to creatinine in the diabetic patients was significantly higher than in the healthy controls (p < 0.01). Moreover, the urinary ratio was found to be gradually increased with the degree of diabetic microangiopathy. Urine molar ratio of sialic acid to creatinine in patients with proliferative diabetic retinopathy was significantly higher than in patients without retinopathy (p < 0.01). Urinary excretion in patients with macroproteinuria was also significantly higher than in patients without nephropathy (p < 0.01). Since urinary levels of sialic acid are proportionally increased with the severity of diabetic microangiopathy, the measurement of urinary sialic acid could become a useful biochemical means to monitor the degree of diabetic microangiopathy.
High Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in the Sultanate of Oman: Results of the 1991 National Survey
Authors: Asfour M. G. , Lambourne A. , Soliman Ashraf , Al‐Behlani S. , Al‐Asfoor D. , Bold A. , Mahtab H. , King H.
Published: July 2009

A national survey of glucose intolerance and cardiovascular disease risk factors in Oman has demonstrated a high prevalence of diabetes (10%) and impaired glucose tolerance (IGT, 13% in females and 8% in males). Prevalence of diabetes rose with age to a maximum of over 30% in both sexes. Prevalence of total glucose intolerance (diabetes and IGT combined) exceeded 50% in the seventh (females) and eighth (males) decade of life.
Cardiovascular Morbidity and Mortality in Type 2 Diabetic Patients: a 22‐year Historical Cohort Study in Dutch General Practice
Authors: de Grauw W.J.C. , van de Lisdonk E.H. , van den Hoogen H.J.M. , van Weel C.
Published: July 2009

A historical cohort study was performed to assess cardiovascular morbidity and mortality in Type 2 (non‐insulin‐dependent) diabetic patients. The data were collected from 1967 to 1989 in four Dutch general practices performing the Continuous Morbidity Registration Nijmegen. Each newly diagnosed Type 2 diabetic patient fulfilling the WHO criteria (n = 265) was matched to a control patient for practice, sex, age, and social class. Inclusion started in 1967, the first year of the still ongoing, Continuous Morbidity Registration Nijmegen. On average, a follow‐up of 6.8 years (range 1 month—22 years) was realized. Compared to the non‐diabetic control patients, the Type 2 diabetic patients showed higher cardiovascular morbidity (risk ratio 1.76, 95 % CI 1.34–2.30) and a higher mortality rate (risk ratio 1.54, 95 % CI 1.07–2.23). Mortality after 10 years was 36 % vs 20 % (p < 0.01), the median survival time 16 years vs 19 years. The cumulative survival rates were significantly different (p < 0.01) between patients and controls in the age group 65–74 years. The higher mortality in Type 2 diabetic patients was completely due to an excess of cardiovascular death (risk ratio 2.05, 95 % CI 1.24–3.37).
Diabetic Retinopathy as a Cause of Blindness in the Province of Turin, North‐west Italy, in 1967–1991
Authors: Porta M. , Tomalino M.G. , Santoro F. , Ghigo L.D. , Cairo M. , Aimone M. , Pietragalla G.B. , Passera P. , Montanaro M. , Molinatti G.M.
Published: July 2009

Diabetes is known to be a major contributor to blindness in industrialized countries but few data are available on the situation in Italy. As an introductory step to the implementation of permanent screening for diabetic retinopathy, a search was carried out on the causes of visual loss in the provincial territory surrounding Turin, the main city of North‐West Italy. The case notes of all 4549 residents in the province who were certified blind between 1967 and 1991 were examined with regard to cause, age at onset, and year of onset of visual acuity 1/20. Diabetic retinopathy was the second commonest cause of bilateral blindness (13.1 % of cases), preceded by cataract (26.7%) and followed by myopia (11.1%), optic atrophy (8.9%), glaucoma (8.9%), retinitis pigmentosa (7.2%), and senile macular degeneration (4.1%). Diabetic retinopathy was the commonest eye disease among those who became blind between the ages of 50 and 70 and remained the leading cause of visual loss when the age groups 20 to 70 were pooled together. The incidence of diabetic retinopathy‐related blindness did not show any trend to decrease over the 25 years investigated. It is concluded that, in spite of widespread availability of facilities for its assessment and treatment, diabetic retinopathy remains a leading cause of blindness in North‐West Italy. This fully justifies the implementation of screening programmes and efficient referral chains for the early detection and prompt treatment of this complication of diabetes.
The Genetic Contribution to Disease Pathogenesis in Childhood Diabetes is Greatest in the Very Young
Authors: Shield J. P. H. , Wadsworth E. J. K. , Baum J. D.
Published: July 2009

Epidemiological data are presented to support the hypothesis that the genetic contribution to disease pathogenesis in childhood onset diabetes is greatest in those presenting at a very early age. Analysis of family data from two national surveys of childhood onset Type 1 (insulin‐dependent) diabetes (1988 in under 15s: 1992 in under 5s) reveals that children developing diabetes between the ages 1 and 2 years are significantly more likely to have a parental history of Type 1 diabetes than older children. It is proposed that compared with other children, those with very early onset diabetes have either a greater genetic and smaller environmental contribution to the initiation of the autoimmune process leading to Type 1 diabetes: or inherited HLA alleles associated with a more fulminant autoimmune mediated Beta‐cell destruction once the process is initiated.