bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Near‐normoglycaemia for 4 Years on Somatic Nerve Dysfunction and Heart Rate Variation in Type 1 Diabetic Patients
Authors: Ziegler D. , Dannehl K. , Wiefels K. , Gries F. A.
Published: July 2009

To evaluate the long‐term effects of near‐normoglycaemia on somatosensory and autonomic nerve dysfunction, 55 poorly controlled Type 1 diabetic patients were allocated to intensified insulin treatment using continuous subcutaneous insulin infusion or multiple insulin injections and were studied prospectively for 48 months. They were divided into three groups according to their mean HbA1 levels during the study. Group 1 (n = 19) had mean HbA1 during months 3–48 in the normal range of <7.8% (near‐normoglycaemic control), Group 2 (n = 18) showed moderately elevated mean HbA1 between 7.8 and 8.5% (satisfactory control), and Group 3 (n = 18) had clearly elevated mean HbA1 of ≥8.6% (poor control). In the three groups studied, the changes in nerve conduction over baseline in the median and peroneal motor nerves as well as median and ulnar sensory nerves after 4 years were inversely related to the mean HbA1 levels of months 3–48 (all p < 0.05). No significant associations with mean HbA1 were noted for the ulnar motor and sural sensory nerve conduction, vibration perception threshold, and heart rate variation. The percentages of patients with neuropathic symptoms decreased from 32 to 14% in Group 1, remained fairly constant in Group 2, and increased from 41 to 73% in Group 3 after 48 months when compared to baseline (p < 0.05). These findings suggest that near‐normoglycaemia maintained for 4 years in Type 1 diabetic patients is associated with increased nerve conduction in the upper limbs and reduced neuropathic symptoms, whereas sensory nerve function in the lower limbs and heart rate variation may remain unchanged. Thus, the potential for improvement in different nerve fibre populations to long‐term improvement in blood glucose control seems to be variable.
Morbidity, Mortality, and Albuminuria in Type 2 Diabetic Patients: a Three‐year Prospective Study of a Random Cohort in General Practice
Authors: Stiegler H. , Standl E. , Schulz K. , Roth R. , Lehmacher W.
Published: July 2009

In a 3‐year prospective study, the prevalence of albuminuria and its relationship to macrovascular disease, pre‐existing vascular risk factors and mortality rate were studied in a random cohort of 290 patients with Type 2 diabetes mellitus in general practice. Newly occurring micro‐ or macroalbuminuria was associated with significantly (p < 0.05) higher systolic blood pressure: median (IQ range) 157 (140–170) vs 150 (130–160) mmHg, in addition to higher serum triglycerides: median (IQ range) 2.71 (1.84–4.25) vs 1.84 (1.35–3.14) mmol I−1, and C‐peptide levels: median (IQ range) 1.30 (0.98–2.16) vs 1.10 (0.82–1.58) nmol I−1, at 3‐year follow‐up. Patients with macroalbuminuria at final examination had significantly higher systolic and diastolic blood pressure, serum triglyceride and β2‐microglobulin levels, decreased HDL‐cholesterol, and a significantly higher prevalence of carotid artery stenoses and peripheral vascular disease. Patients dying from vascular causes showed significantly higher urinary albumin levels at entrance as compared to the surviving patients: median (IQ range): 42.2 (11–249.7) vs 10.4 (4.6–28.0) mg I−1, p < 0.008, and overall mortality rate was significantly linked with the presence of macroalbuminuria (26% vs 5% in normoalbuminuric patients). A comparison between the results of the initial and the final examination indicated an overall worsening of renal variables (albuminuria: median (IQ range): female 9.5 (4.5–21) vs 13.4 (5.1–39.7) mg I−1, (p < 0.05); male 13.8 (4.7–34.1) vs 32.6 (8.1–78.7) (p < 0.001), despite a significant improvement in metabolic variables. At the same time, a significant increase of the prevalence of peripheral vascular disease (female 41 vs 59%, p<0.005; male 35 vs 47%, p < 0.05; 95% confidence interval: female 33–49% vs 51–67%; male 25–46% vs 36–58%) and stenoses of the carotid artery (female 8.6 vs 18%, p < 0.05 and male 4.8 vs 16%, p < 0.005, 95% CI: female 4.8–14% vs 12.4–24.8%, male 1.3–11.9 vs 8.8–25.9) was found. Macroalbuminuria in particular appears to be a marker of peripheral vascular disease accompanied by a number of risk factors commonly seen in the context of Syndrome X, and predicts macrovascular deaths.
Influence of Ripeness of Banana on the Blood Glucose and Insulin Response in Type 2 Diabetic Subjects
Authors: Hermansen K. , Rasmussen O. , Gregersen S. , Larsen S.
Published: July 2009

Banana is a popular and tasty fruit which often is restricted in the diet prescribed for diabetic patients owing to the high content of free sugars. However, in under‐ripe bananas starch constitutes 80–90% of the carbohydrate content, which as the banana ripens changes into free sugars. To study the effect of ripening on the postprandial blood glucose and insulin responses to banana, 10 type 2 (non‐insulin‐dependent) diabetic subjects consumed three meals, consisting of 120 g under‐ripe banana, 120 g over‐ripe banana or 40 g white bread on separate days. The mean postprandial blood glucose response area to white bread (181 ± 45 mmol I−1× 240 min) was significantly higher compared with under‐ripe banana (62 ± 17 mmol I−1× 240 min:p< 0.01) and over‐ripe banana (106 ± 17 mmol I−1× 240 min:p< 0.01). Glycaemic indices of the under‐ripe and over‐ripe bananas differed (43 ± 10 and 74 ± 9:p< 0.01). The mean insulin response areas to the three meals were similar: 6618 ± 1398 pmol I−1× 240 min (white bread), 7464 ± 1800 pmol I−1× 240 min (under‐ripe banana) and 8292 ± 2406 pmol I−1× 240 min (over‐ripe banana). The low glycaemic response of under‐ripe compared with over‐ripe bananas may be ascribed to the high starch content, which has previously been found to be only hydrolysed slowly by alfa‐amylase in humans. In conclusion, bananas, particularly under‐ripe, contain low glycaemic carbohydrates which are a cheap source of carbohydrate and an acceptable alternative as between‐meal snacks for Type 2 diabetic subjects.
Relationship Between Insulin Injection Regimen and Metabolic Control in Young Danish Type 1 Diabetic Patients
Authors: Mortensen H.B. , Villumsen J. , Vølund Aa. , Petersen K.E. , Nerup J. ,   The Danish Study Group of Diabetes in Childhood
Published: July 2009

In 1987 and 1989 nationwide screening for HbA1c was carried out in Denmark. Twenty‐one paediatric departments treating children with diabetes participated in the first study and twenty‐two in the second. During this 2‐year period metabolic control deteriorated despite the fact that the use of multiple injection regimens increased from 39% to 54%. The possible reasons for the deterioration in metabolic control were examined in the 429 children (≥9 years, 1987) and adolescents (<18.8 years, 1989) who participated in both studies. All had diabetes duration of greater than one year (1987) and all were treated by the same departments during the study period. The children were divided into three subgroups according to injection regimen. Group A (n=128) received twice‐daily insulin injections; group B (n=171) were on multiple injections (three or more) while group C (n=130) shifted from twice‐daily insulin to multiple injections during the 2‐year period. A deterioration of blood glucose control as assessed by HbA1c was observed in all three treatment groups. For group C the 2‐year increase in daily insulin dose was more pronounced for males (19%) than for females (6%). Body mass index increased significantly in all treatment groups during the study period. The 1989 mean levels were higher in group B (males 20.6 kg m−2, females 22.0 kg m−2) than group A (males 19.3 kg m−2, p=0.002; females 20.7 kg m−2, p=0.000003) and group C (males 19.4 kg m−2, p=0.0005; females 20.7 kg m−2, p=0.008). Growth velocity was reduced for both sexes in group B compared to group A and C (males, p=0.0005; females, p=0.007). In conclusion all subgroups showed a deterioration of metabolic control from 1987 to 1989. Even the group changing from twice daily insulin to three or more injections did not improve blood glucose control.
Benefits Provided by an Integrated Education and Clinical Diabetes Centre: A Follow‐up Study
Authors: Day J.L , Metcalfe J. , Johnson P.
Published: July 2009

The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purposed design diabetes centre, on diabetes control, attendance and cancellation rates, and admission for diabetic emergencies have been reviewed. Glycaemic control was examined in: (a) a cohort of 163 insulin‐treated and 47 non‐insulin treated diabetic subjects (age < 65 years) studied prospectively before and 3 years following the introduction of a new system of care; (b) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over; (c) a cross‐sectional study of the clinic population (n = 700) the year before and 3 years after the changeover; (d) a group of patients attending standard unaltered clinics in the same district (n = 157). Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre, with the means for those aged less than 65 falling from 11.9 ± 2.3% to 9.9 ± 1.9% and for those aged over 65 from a mean of 11.7 ± 2.0% to 10.3 ± 2.3%, 3 years later. The cross‐sectional study provided similar results with a mean HbA1 of 12.2 ± 3.0% prior to changeover and 10.4 ± 4.4%, 3 years later. Smaller but significant changes were observed in patients continuing to attend the routine clinic (from 12.2 ± 2.3% to 11.3 ± 2.6%) over a similar period. Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23, to 33 and 5 per annum, respectively. Failed to attend rates prior to changeover were 14% of the total appointments and fell to 5.7% 4 years later. We conclude that improvement in standards of diabetic control can be achieved by close integration of education and clinical management.
Gestational Diabetes: A Challenge For The Future
Authors: Dornhorst A. , Beard R.W.
Published: July 2009

It is well established that pregnancy is associated with temporary changes in maternal metabolism which include a decrease in maternal insulin sensitivity to values similar to those associated with Type 2 diabetes. Fasting glucose concentrations fall throughout pregnancy, postprandial values rise. The maintenance of glucose tolerance in pregnancy requires a two‐ to three‐fold increase in postprandial maternal insulin secretion. Glucose intolerance develops in women unable to compensate for the metabolic changes incurred by pregnancy. Increasing maternal hyperglycaemia is associated with increasing pregnancy morbidity and an increased likelihood of subsequent diabetes in the mother. In addition, maternal hyperglycaemia has a direct effect on the development of the fetal pancreas and is associated with an increased susceptibility to future diabetes in the infant, an effect which is independent of genetic factors. Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized in pregnancy, and by definition includes a small number of women with previously unrecognized diabetes or impaired glucose tolerance (IGT). Figures on the prevalence of GDM vary between maternity units, depending on screening methods and the ethnic distribution of the populations. However, in a comprehensive study of a multi‐ethnic antenatal population in inner London, UK it was found that only 2% of pregnant women develop significant glucose intolerance. Obstetricians and physicians debate the importance of identifying this 2% of women. The lack of agreed criteria for diagnosing gestational diabetes and the questionable obstetric benefits of treating all women with mild disturbances of glucose tolerance in pregnancy has resulted in few UK centres undertaking universal screening for GDM. This review examines the potential benefits arising from the diagnosis of gestational diabetes, both for pregnancy outcome in the short term and for the health of the mother and child in the long term.
Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration
Authors: Stevens M. J. , Goss D.E. , Foster A.V.M. , Pitei D. , Edmonds M.E. , Watkins P.J.
Published: July 2009

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non‐diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non‐ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non‐diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated.

One hundred and eight non‐insulin‐dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re‐evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow‐up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min−1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.
What do People with Diabetes Want to Talk About With Their Doctors?
Authors: Benett I.J.
Published: July 2009

A survey was conducted to establish the concerns of people with diabetes when they consult their doctors. A total of 225 people attending consecutively at the Manchester Diabetes Centre were invited to take part. Their concerns were assessed by a questionnaire administered immediately before consulting a doctor. Of the 220 (98%) respondents 53.6% had concerns about metabolic control; 31.8% had concerns which suggested cognitive or emotional problems in coming to terms with their diabetes; 20.5% and 22.7% had concerns related to organ involvement and medication, respectively; 11.8% expressed no concerns. Women who were concerned about metabolic control and organ involvement were younger than women who were not (p < 0.001, and p = 0.004, respectively). Men who were concerned about medication were younger than men who were not (p = 0.002). The concerns of men diagnosed for ≦ 10 years were more likely to suggest difficulty in adjusting to the disease than those who had been diagnosed for longer (p = 0.007). Women diagnosed for ≦ 10 years were more likely to be concerned about metabolic control than those diagnosed for longer (p = 0.018). Both men and women diagnosed for > 10 years, were more likely to be concerned about medication than those diagnosed for a shorter time (p = 0.025). Ethnicity did not seem to influence the outcomes. The significant proportion of people who have concerns which suggest difficulty in adjusting to the disease, the gender differences, and the changes over time suggest the need for more detailed research into those concerns.
Long‐term Effect of Acarbose on Glycaemic Control in Non‐insulin‐dependent Diabetes Mellitus: A Placebo‐controlled Double‐blind Study
Authors: Hotta N. , Kakuta H. , Sano T. , Matsumae H. , Yamada H. , Kitazawa S. , Sakamoto N.
Published: July 2009

The efficacy and safety of acarbose therapy (100 mg tds for 24 weeks) was investigated in a placebo‐controlled double‐blind study in patients with non‐insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone. In the acarbose group, the 2 h postprandial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l−1 to 11.3 mmol l−1 and from 11.1 % to 9.7 %, respectively. In the placebo group, the 2 h postprandial blood glucose (14.4 mmol l−1 to 14.2 mmol l−1) and the hemoglobin A1 level (10.3% to 9.9%) showed no significant changes. A 75 g oral glucose tolerance test was performed before and after the study, the difference not being significant in either the acarbose group or the placebo group. The incidence of side‐effects (mainly gastrointestinal symptoms such as flatulence and abdominal distension) was high at 78.9 % in the acarbose group and 61.1 % in the placebo group. However, there was no significant difference between the groups, and side‐effects in the acarbose group tapered during the trial, suggesting that some at least were not related to the drug. From these findings, it was concluded that acarbose is an effective new treatment for diet treated non‐insulin‐dependent diabetic patients.
Hypoglycaemic Admissions Among Diabetic Patients in Soweto, South Africa
Authors: Gill G.V. , Huddle K.R.
Published: July 2009

An audit of hypoglycaemic admissions among diabetic patients to Baragwanath Hospital, Soweto, South Africa was carried out prospectively during a recent 5‐month period. A total of 51 episodes of biochemically confirmed hypoglycaemia (blood glucose < 2.2 mmol I−1 with coma or pre‐coma, and requiring intravenous glucose) were observed in 43 patients. There was a wide range of ages (22–88 years) and an excess of males (27M:16F). Fourteen (33%) cases were associated with sulphonylurea (gliclazide) treatment. Doses of insulin or sulphonylureas were not excessive. The major cause precipitating the event was a missed meal (36 %), though alcohol (22 %), gastrointestinal upset (20%), and inappropriate treatment (18%) were also important contributory factors. Following recovery from the event, doses of drugs or insulin were frequently reduced, and three patients were successfully taken off insulin, and six off gliclazide. There was no mortality in this series, and no obvious long‐term morbidity. We conclude that severe hypoglycaemia is a frequent and important acute diabetic complication in Soweto. Patient education and care in prescribing for Type 2 diabetic patients may help reduce its occurrence and severity.
An Analysis of the Glucagon Response to Hypoglycaemia in Patients with Type 1 Diabetes and in Healthy Subjects
Authors: Liu D. , Adamson U. , Lins P.‐E. , Clausen‐Sjöbom N.
Published: July 2009

The study aimed to analyse the glucagon response during hypoglycaemia in relation to gender, level of hypoglycaemia, and hyperinsulinaemia as well as its relation to other counterregulatory hormones in patients with Type 1 diabetes and in nondiabetic subjects. Mild hypoglycaemia was induced by an i.v. insulin infusion (244 pmol kg−1h−1) for 180 min in 43 Type 1 diabetic patients and 22 nondiabetic subjects. Venous blood glucose, plasma free insulin, glucagon, adrenaline, noradrenaline, growth hormone, and cortisol were measured every 15–30 min. The hormonal responses during hypoglycaemia were evaluated from the incremental areas under their respective curves. There was a linear correlation between the glucagon response and the decremental area of blood glucose (p < 0.005), but the slope of the regression line in the diabetic group was less steep than in the controls (p < 0.5), and, in spite of the deeper hypoglycaemia in the diabetic groups, their glucagon response was diminished (p < 0.05). Plasma, adrenaline, growth hormone and cortisol all increased during hypoglycaemia. The glucagon response correlated with the responses of growth hormone and cortisol in both groups, while it was positively correlated with the adrenaline response (p < 0.001) and inversely with the plasma insulin (p < 0.001) only in the diabetic patients. Although the insulin infusion rate was identical, the female diabetic patients had a lower metabolic clearance rate of insulin as compared with the males (p < 0.05). There was no statistical difference in the counterregulatory hormone responses between males and females in neither of the groups. In conclusion, this study suggests that the glucagon response to hypoglycaemia in Type 1 diabetic patients, may be suppressed by circulating insulin within its therapeutic range, and stimulated by the simultaneously secreted adrenaline. Furthermore, female Type 1 diabetic patients have a lower metabolic clearance rate of insulin than males, yielding a more pronounced hypoglycaemia in response to the same dose of insulin, although this study does not provide evidence of a gender difference in the responsiveness of counterregulatory hormones to hypoglycaemia.
Outcome of Pregnancy in Diabetic Women in Soweto, South Africa 1983–1992
Authors: Huddle K. , England M. , Nagar A.
Published: July 2009

A specialized service for pregnant diabetic women of African ethnic origin from Soweto was introduced in May 1983 at Baragwanath Hospital. Modern methods of management were used, including home blood glucose monitoring. A total of 354 pregnancies (147 gestational, 207 pregestational) were managed over an 8 1/2 year period. All but 12 women were treated with insulin. Mean capillary blood glucose (± SD) ranged from 5.8 ± 0.8 mmol l−1 in the insulin‐dependent group to 6.2 mmol l−1 in the gestational group (p<0.01). Although maternal hypoglycaemia was common (14.4%) in the insulin‐dependent patients, no ill effects were noted. The highest Caesarean section rate was in the gestational group (56%), the lowest in the insulin‐dependent group (39.8%) (p < 0.01). Mean (±SD) neonatal weights were similar in the insulin‐dependent and non‐insulin‐dependent groups (3131 ± 627.9 g and 3236 ± 674.3 g resp. p = NS); offspring of the gestational group were heavier than the insulin‐dependent group (3384.4 ± 657.5 g) (p < 0.01). Neonatal hypoglycaemia occurred in less than 5% of offspring overall. The combined perinatal mortality was 6.1%, stillbirths accounting for the majority (63.6%) of deaths. Major congenital abnormalities occurred in 6(1.7%) of the offspring. The perinatal mortality of the ‘control’ group of 146 women was 26.1%. Glucose intolerance persisted in at least 34.7% of gestational diabetic women postpartum. This study suggests that a specialized service for pregnant diabetic women from a Third World community can be implemented with good effect and limited expense. Late presentation of pregestational diabetic women is a problem.
Insulin Deficiency and Increased Plasma Concentration of Intact and 32/33 Split Proinsulin in Subjects with Impaired Glucose Tolerance
Authors: Davies M.J. , Rayman G. , Gray I.P. , Day J.L. , Hales C.N.
Published: July 2009

In order to determine insulin status and beta cell function during the oral glucose tolerance test (OGTT), in impaired glucose tolerance (IGT), 51 such subjects and matched controls, identified during a population survey for diabetes, underwent a 75 g OGTT. Fasting, 30 min and 2 h insulin and intact proinsulin, and fasting and 2 h 32/33 split proinsulin, were measured by specific two‐site immunoradiometric assays. The subjects with IGT had higher fasting (geometric mean ± SD, 5.0 ± 4.0 pmol−1 vs 2.9 ± 1.7, p < 0.02) and 2 h intact proinsulin (23 ± 14 vs 14 ± 12, p < 0.0001), and fasting (3.2 ± 3 pmol−1 vs 1.8 ± 1.8, p < 0.0007) and 2 h 32/33 split proinsulin (18.3 ± 19 pmol−1 vs 6.6 ± 15, p < 0.0001). Despite higher plasma glucose concentrations, the IGT group had similar fasting insulin, lower 30 min insulin (216 ± 124 pmol−1 vs 278 ± 130, p < 0.02), and a lower 30 min insulin/glucose ratio (23.7 ± 2.1 vs 34.8 ± 2.3, p < 0.002). The percentage of fasting proinsulin‐like to total insulin‐like molecules was higher in those with IGT (15.3 ± 8% vs 11.6 ± 8, p < 0.04). After 6 months, at repeat OGTT, the same subjects with IGT were classified as ‘persisters’ or ‘reverters’. The persister (24/51 47.1%), at initial OGTT, had a higher 2 h glucose level, a greater BMI and higher systolic blood pressure, but other parameters were similar to the reverters. In the reverters, when baseline variables were compared to those recorded at six month follow‐up, there was a reduction in 2 h intact (23.8 ± 13 pmol−1 vs 19.4 = 10, p < 0.02) and 32/33 split proinsulin (20.4 ± 18 pmol−1 vs 13.8 ± 13, p < 0.006), and an increase in fasting insulin (41 ± 30 pmol−1 vs 54 ± 35, p < 0.02), respectively, despite no change in fasting glucose. These findings show that IGT is associated with beta cell dysfunction and reduced early insulin secretion during the OGTT. In some subjects with IGT these abnormalities show improvement in the short term.
Thrombin Generation and Factor VIII:C Levels in Patients with Type 1 Diabetes Complicated by Nephropathy
Authors: Ibbotson S.H. , Rayner H. , Stickland M.H. , Davies J.A. , Grant P.J.
Published: July 2009

The association between plasma coagulant activity and the presence of diabetic nephropathy was investigated in 31 patients with Type 1 diabetes, 12 with and 19 without nephropathy, and in 11 healthy subjects. Thrombin generation was assessed by computer assisted chromogenic method and expressed as time (in seconds) to 50% maximal thrombin activity (T50). Factor VIII:C levels related to thrombin activity, glycaemic control, and renal function. Median (IQ) FVIII:C concentration was increased in patients with nephropathy (1590 (1130–1900) IU l−1) compared to those without renal disease and with controls (960 (750–1090); 1020 (810–1100) IU l−1, p < 0.01, respectively). There were no significant differences in T50 values between the groups. FVIII:C correlated with age in all subjects and in the diabetic group (r = 0.33, p = 0.036; r = 0.39, p = 0.031) and inversely with T50 in all subjects and in controls (r = −0.35, p = 0.02; r = −0.62, p = 0.04). In all subjects and in patients, FVIII:C was related to urinary albumin excretion and creatinine clearance. FVIII:C and T50 were not related to HbA1c. The results show that FVIII:C levels are increased in Type 1 diabetes complicated by nephropathy and are related to degree of renal impairment but not levels of glycaemia. No associated enhancement of plasma procoagulant activity was detected.
Differential Metabolic Actions of Biosynthetic Insulin Analogues in Normal Man Assessed by Stable Isotopic Tracers
Authors: Gelding S. V. , Coldham N. , Anyaoku V. , Heslop K. , Halliday D. , Johnston D. G.
Published: July 2009

Insulin analogues have been produced with high affinity for the insulin receptor and with affinity lower than that of native insulin, but differences in activity when administered in vivo to man are unconvincing. We have used very low dose insulin (0.005 units kg−1 h−1) to investigate possible differences in effect of these insulin analogues on lipolysis in seven healthy subjects. Only minor effects on blood glucose concentration were observed and glucose turnover measured isotopically with 6,6 2H glucose and leucine turnover measured with 1−13C leucine did not change significantly. Fatty acid levels decreased with insulin (area under curve, median (range) −23 (‐41–10) mmol l−1 h) and with the low affinity analogue (‐28 (‐42–19) mmol l−1 h), but the high affinity analogue had no significant effect compared with controls (high affinity analogue −8 (‐28–35) mmol l−1 h; control +15 (11–53) mmol l−1 h). Glycerol production measured isotopically decreased with insulin (‐0.54 (‐1.50–0.63) μmol kg−1 min−1) and with the low affinity analogue (‐0.74 (‐1.76–0.72) μmol kg−1 min−1), but the high affinity analogue at these doses had no significant effect on glycerol turnover (‐0.19 (‐0.74–1.13) μmol kg−1 min−1). Thus at these low infusion rates insulin itself and the low affinity analogue suppressed lipolysis, as assessed by glycerol turnover and by circulating fatty acid concentrations. The high affinity analogue was cleared rapidly from the circulation producing no measurable increase in immunoreactive insulin concentrations, and no effect was observed on lipolysis.
The Degree of Day‐to‐day Variation in Food Intake in Diabetic Patients
Authors: Close E.J. , Wiles P.G. , Lockton J.A. , Walmsley D. , Oldham J. , Wales J.K.
Published: July 2009

A prospective study of food intake using 7 day food diaries was undertaken in 92 diabetic men and women aged 17–81 years. The median individual day‐to‐day coefficients of variation for energy intake were: in insulin treated patients 12.0%, in non‐insulin treated patients 13.7%; for carbohydrate intake 14.5% and 13.8% and for fat 20.7% and 20.8%, respectively. The median individual differences between the minimum and maximum daily intake of energy in insulin treated patients was 787 kcal, in non‐insulin treated patients 649 kcal, for carbohydrate intake 89g and 77g and for fat 50g and 43g, respectively. Only 39% patients ate within 20% of their prescribed carbohydrate diet. In non‐insulin treated patients on prescribed calorie controlled diets, calorie consumption was on average 46% in excess of that prescribed. Although the variation in dietary intake in diabetic patients is large, it is smaller than that reported in non‐diabetic subjects in the UK. This variation is likely to make the manipulation of other antidiabetic therapy both difficult and somewhat arbitrary.
Pregnancy is Not a Risk Factor for a Deterioration of Autonomic Nervous Function in Diabetic Women
Authors: Airaksinen K.E.J. , Salmela P.I.
Published: July 2009

Pregnancy may have an untoward effect on diabetic retinopathy and nephropathy and symptoms of autonomic neuropathy may also be exacerbated during pregnancy. To test the hypothesis that previous pregnancies during the diabetic state are associated with increased risk of development of autonomic dysfunction, autonomic nervous function and pregnancy history were assessed in 117 women with long‐standing Type 1 diabetes mellitus. Thirty‐eight women (32 %) had autonomic dysfunction, defined as at least one abnormal cardiovascular test. The presence of autonomic dysfunction was not related to the number of pregnancies during the disease state. Thus, this cross‐sectional study suggests that pregnancies do not represent a risk factor for a deterioration of autonomic nervous function and development of autonomic neuropathy in diabetic women.
A Prospective Study of Clinical and Metabolic Associates of Proteinuria in Patients with Type 2 Diabetes Mellitus
Authors: Niskanen L. , Voutilainen R. , Teräsvirta M. , Lehtinen J. , Teppo A.‐M. , Groop L. , Uusitupa M.
Published: July 2009

Urinary protein excretion rate and clinical and metabolic associates were investigated in a group of 108 patients with Type 2 diabetes mellitus at the time of diagnosis and after 5 years, and also 121 control subjects. The presence of coronary heart disease, neuropathy and retinopathy, cardiovascular risk factors and 24‐h urinary excretion rate of albumin, beta‐2‐microglobulin, and IgG were examined. At the 5‐year examination, urinary excretion rate of albumin was higher in diabetic patients than in control subjects (39 ± 75 vs 16 ± 28 mg 24 h−1 for men, p < 0.05; 38 ± 57 vs 22 ± 42 mg 24−1 h for women, p < 0.01). Furthermore, increased beta‐2‐microglobulin excretion rate, a marker of tubular impairment, was observed in diabetic men as compared to control men (0.17 ± 0.15 vs 0.14 ± 0.21 mg 24 h−1, p < 0.05). Diabetic patients with increased albumin excretion rate (> 30 mg 24 h−1) showed poorer metabolic control than those with normal albumin excretion rate, but no significant differences in body mass index or in the frequencies of smoking, hypertension, coronary heart disease or retinopathy and neuropathy were observed between the groups. Baseline hyperinsulinaemia was closely associated with increasing albuminuria at the 5‐year examination.
The Five‐year Incidence of Blindness after Introducing a Screening Programme for Early Detection of Treatable Diabetic Retinopathy
Authors: Agardh E. , Agardh C.‐D. , Hansson‐Lundblad C.
Published: July 2009

The incidence of moderate visual impairment and blindness due to diabetic retinopathy was studied 5 years after introducing a screening system for early detection of treatable retinopathy. Photocoagulation was performed in patients with clinically significant macular oedema, severe preproliferative, and proliferative retinopathy. Eighty‐eight percent of 470 Type 1 and 88 % of 388 Type 2 diabetic patients were still available for follow‐up. In the Type 1 group, the five‐year incidence of blindness and moderate visual impairment were 0.5 % and 1.2 %, respectively. Corresponding figures for the Type 2 diabetic patients were 0.6 % and 1.7 %, respectively. The majority of patients with loss of vision had severe retinopathy at baseline. Among those who entered the screening programme with no or mild retinopathy, loss of vision occurred in only one of the Type 1 and four of the Type 2 diabetic patients. It is concluded that the risk for visual impairment and blindness due to diabetes can be substantially reduced by using programmes for early detection of and effective treatment of diabetic retinopathy.
An Approach to the Use of the DO IT Study Group Guidelines for Supporting the Optimal Implementation of Information Systems in Diabetes Care
Authors: Flack J.R. , Home P.D.
Published: July 2009

The usefulness of the 1992 DO IT Study Group guidelines for diabetes data information systems was assessed using two established diabetes databases designed for different purposes. The recommendations detailed in the guidelines, written in four separate but overlapping modules, were applied individually to each database in turn. Percentage compliance with the recommendation to collect the DiabCare dataset was high, after discounting specialist areas. While on the whole the information systems complied with the guidelines within the purposes for which they were designed, areas highlighted as demanding further action in at least one of the two systems included password protection, data validation checks, screen design, and communication with those whose records were held on the systems. Application of the guidelines is already stimulating attention to some of these areas. Some of the guidelines proved rather vague in construction to be applied in any formal sense, while others (for example in relation to international accreditation of datasets) were not applicable to individual systems. The results suggest the importance of a structured approach to the design, development, and ongoing assessment of information systems in diabetes, but require the present guidelines to develop a more formal structure to be fully effective. The widespread adoption and further testing and refinement of these guidelines (both within and outside Europe) should promote the ultimate goal of improved diabetes care.
Difficulties in Classifying Diabetes at Presentation in the Young Adult
Authors: Arnqvist H.J. , Littorin B. , Nyström L. , Scherstén B. , Östman J. , Blohmé G. , Lithner F. , Wibell L.
Published: July 2009

All newly diagnosed diabetic patients in Sweden aged 15–34 years have been registered since 1983. In this study the clinical characteristics initially and after 2.5‐3 years were evaluated by a questionnaire to the patient's physician and by non‐fasting C‐peptide. The study comprised patients registered 1983‐84, and for 281 patients (37%), complete information was obtained. At diagnosis 75% were classified as Type 1, 19% as Type 2, and 6% as secondary diabetes or as uncertain by their physician. Twenty patients (7.1%) were reported to have ketoacidosis. Seventy‐five percent were treated with insulin, 7% with oral hypoglycaemic agents (OHG), and 18% with diet alone. At follow‐up 71% were classified as Type 1, 21% as Type 2, and 8% as secondary or uncertain while treatment was 82% insulin, 8% OHG, and 9% diet. During the follow‐up period 42% of the initially non‐insulin‐treated patients were put on insulin whereas only a few stopped insulin treatment. Patients treated with diet or OHG at follow‐up were older, had higher percent desirable weight, and lower blood glucose at diagnosis than patients treated with insulin. All except one patient had measurable random C‐peptide at follow‐up and mean values were for patients treated with insulin 0.55, OHG 1.41 and diet alone 1.29 nmol I−1. Random blood glucose results were similar. In conclusion the majority of newly diagnosed patients in the age group 15–34 years have the characteristics of Type 1 diabetes and Type 2 diabetes is rare before 25–30 years of age. Patients with biochemically mild hyperglycaemia are difficult to classify and there is a need for new guidelines for classification of diabetes which include aetiopathogenetic aspects.
Comparison of Platelet Aggregability in Japanese Type 2 Diabetic Patients With and Without Microalbuminuria
Authors: Baba T. , Kodama T. , Yasuda T.K. , Ishizaki T.
Published: July 2009

Microalbuminuria is associated with higher cardiovascular morbidity and mortality in Type 2 (non‐insulin‐dependent) diabetic patients. This study was designed to assess whether Type 2 diabetic patients with microalbuminuria (urinary albumin excretion rate (AER) 20–200 μg min−1) is associated with alterations in platelet aggregability as compared with those with normal urinary albumin excretion (AER < 20 μg min−1). Platelet aggregability was compared between 21 Japanese Type 2 diabetic patients with microalbuminuria and 21 individually pair‐matched (for age, sex, body mass index, treatment, and HbA1c level) patients with normoalbuminuria. The in vitro platelet aggregation induced by 1.0 and 3.0 μmol I−1 ADP and 0.5 and 1.0 mg I−1 collagen was measured using platelet‐rich plasma. No significant differences were observed between the two groups in the values for maximum percent platelet aggregation, percent aggregation at 3 min, and aggregation velocities after adding ADP or collagen. Microalbuminuric patients had significantly higher mean values for systolic (p < 0.004) and diastolic (p < 0.02) blood pressures and plasma fibrinogen level (p < 0.03) as compared with the respective mean values in normoalbuminuric patients. The results suggest that Japanese microalbuminuric Type 2 diabetic patients do not differ in the degree of platelet aggregability as compared with normoalbuminuric patients, despite an increase in certain other coronary risk factors.
The Effect of Intensive Insulin Therapy on the Insulin‐regulatable Glucose Transporter (GLUT4) Expression in Skeletal Muscle in Type 1 Diabetes
Authors: Andersen P.H. , Vestergaard H. , Lund S. , Vedel P. , Junker S. , Kahn B.B. , Pedersen O.
Published: July 2009

Studies in normal man and rodents have demonstrated that the expression of the dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin at supraphysiological circulating levels. The present study was designed to determine whether intensified insulin replacement therapy for 24 h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble insulin for 24 h the fasting plasma glucose concentration decreased from 20.8 ± 2.3 (SD) to 8.7 ± 2.3 mmol 1−1 whereas the fasting serum insulin level increased from 0.06 ± 0.02 to 0.17 ± 0.09 nmol 1−1 However, despite a 2.8‐fold increase in serum insulin levels and more than a halving of the plasma glucose concentration for at least 15 h no significant alterations occurred in the amount of GLUT4 protein (0.138 ± 0.056, poor control vs 0.113 ± 0.026 arb. units, improved control, p = 0.16) or GLUT4 mRNA (96432 ± 44985, poor control vs 81395 ± 25461 arb. units, improved control, p = 0.54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short‐term regulation of GLUT4 expression in Type 1 diabetic patients.
Necrobiosis Lipoidica Diabeticorum: Association with Background Retinopathy, Smoking, and Proteinuria. A Case Controlled Study
Authors: Kelly W.F. , Nicholas J. , Adams J. , Mahmood R.
Published: July 2009

In order to evaluate patients with necrobiosis lipoidica diabeticorum and to compare them with age, sex, and duration of diabetes matched controls, 15 patients with necrobiosis were each matched with 5 control subjects with diabetes mellitus. Complications of diabetes, glycaemic control, and proteinuria were measured. Patients with necrobiosis (mean age 40, range 18–74 years) had a mean duration of diabetes of 14 (range 3–36) years; 8 patients were male, and 7 were female. For necrobiosis versus controls, background retinopathy (67% vs 27%, p = 0.009), proteinuria (53% vs 17%, p = 0.006), and smoking (60% vs 20%, p = 0.003) were all more common with necrobiosis. There were no significant differences between patients with necrobiosis and control patients in the prevalence of vascular disease and neuropathy. Glycosylated haemoglobin concentrations were higher in patients with necrobiosis (p = 0.02). Blood pressure measurements were similar in both groups. We conclude that smoking, proteinuria, and retinopathy were more prevalent in diabetic patients with necrobiosis; the skin lesion may therefore share common aetiological factors which affect the microvascular circulation, leading to damage to basement membranes and vascular endothelial cells.
Decreased Plasminogen Activator Inhibitor‐1 Activity in Newly Diagnosed Type 2 Diabetic Patients Following Dietary Modification
Authors: Bahru Y. , Kesteven P. , Alberti K.G.M.M. , Walker M.
Published: July 2009

Increased plasminogen activator inhibitor‐1 (PAI‐1) activity has been reported in Type 2 (non‐insulin‐dependent) diabetes and is a recognized risk factor for coronary artery disease. Fourteen newly diagnosed Type 2 diabetic patients were studied before and 3 months after standard clinical dietary modification. To assess the effect of improved metabolic control on PAI‐1 activity, nine Type 2 diabetic patients established on diet therapy and with previous stable glycaemic control served as controls. In the newly diagnosed patients diet therapy resulted in a significant decrease in HbA1c levels (8.3 ± 0.5 vs 5.2 ± 0.3 % (mean ± SEM); p < 0.001), and this was accompanied by a fall in fibrinogen (4.3 ± 0.3 vs 3.0 ± 0.2 g.1−1; p < 0.01) concentration, and PAI‐1 (18.7 ± 2.3 vs 12.2 ± 0.9 arbitrary units ml−1; p < 0.02) and factor VIII (147 ± 17 vs 115 ± 13 %; p < 0.01) activities. PAI‐1 activity was correlated with triglyceride levels at the first assessment in the newly diagnosed patients (r = 0.66; p < 0.01), and this was the only independent association by multiple regression analysis when all patients (n = 23) were considered (r = 0.62; p < 0.002). However, there was no association between the changes in PAI‐1 activity and the changes in HbA1c BMI, and serum triglyceride levels following treatment in the newly diagnosed patients. Serum triglyceride concentrations, HBA1c, PAI‐1 activity, and the coagulation factors remained unchanged in the control group over the same treatment period. In conclusion, the introduction of conventional diet therapy in newly diagnosed Type 2 diabetic patients was accompanied by a significant improvement in circulating PAI‐1 activity, but this could not be related to changes in the common indices of metabolic control.
Fasting Plasma Glucose in the Diagnosis of Diabetes Mellitus: A Study from Southern India
Authors: Ramachandran A. , Snehalatha C. , Vijay V. , Viswanathan M.
Published: July 2009

The usefulness of fasting plasma glucose (FPG) in the diagnosis of diabetes mellitus was assessed in Asian Indians in South India. Oral GTT values in 570 newly screened adults were studied. Taking the WHO criteria of 2 h plasma glucose (PG) of ≥ 11.1 mmol l−1 for diagnosis of diabetes, the validity of a FPG of ≥ 7.8 mmol l−1 cut off value for diabetes was assessed. Using the regression analysis, the correlations of the FPG to 2 h PG were examined. Among the 268 with 2 h PG value of ≥ 11.1 mmol l−1, 205 (76.5 %) had FPG ≥ 7.8 mmol l−1. Sensitivity of FPG was 76.5 % for diagnosis of diabetes and its specificity was 99 %. An exponential regression model gave the best fit for FPG vs 2 h PG and using the regression equation, the predicted FPG for a 2 h PG of 11.1 mmol l−1 was 7.05 mmol l−1. Sensitivity increased to 90.3 % with FPG of 7.05 mmol l−1 while the specificity remained at 92 %. It is concluded that in the south Indian subjects, the sensitivity for diagnosis of diabetes with FPG of ≥ 7.8 mmol l−1 was 76.5 %; and it increased to 90.3 % with FPG of ≥ 7.05 mmol l−1.
Mortality in Diabetic Patients with Cardiovascular Autonomic Neuropathy
Authors: Rathmann W. , Ziegler D. , Jahnke M. , Haastert B. , Cries F.A.
Published: July 2009

Cardiovascular autonomic diabetic neuropathy (CADN) may carry an increased risk of mortality. However, in previous studies the prognosis of patients with CADN seemed to be influenced by life‐threatening macro‐ and microvascular complications which had already been present at the start of the study period. Between 1981 and 1983, 1015 diabetic patients have been examined for CADN (abnormal heart rate variation at rest and during deep respiration) at the Diabetes Research Institute, Düsseldorf. Thirty‐five patients (28 with Type 1 diabetes, 7 with Type 2 diabetes) with CADN have been retrospectively recruited and reviewed 8 years later and compared with 35 patients without CADN who were matched for sex, age, and duration of diabetes. Exclusion criteria for entry into the study included severe micro‐ or macrovascular complications, such as proliferative retinopathy, proteinuria or symptomatic coronary artery disease. During the 8‐year observation period, 8 patients with CADN and 1 patient without CADN died. The survival rate estimates steadily declined in patients with CADN over the whole period studied. The 8‐year survival rate estimate in patients with CADN was 77 % compared with 97 % in those with normal autonomic function (p < 0.05). Deaths were mainly due to macrovascular diseases (n = 3) and sudden unexpected deaths (n = 3). One patient with CADN died after an episode of severe hypoglycaemia. Among the deceased patients, coefficient of variation of R‐R intervals during deep breathing was significantly reduced when compared with those who survived (1.04 ± 0.5 % vs 1.87 ± 1.0 %; p < 0.05), and symptoms of autonomic neuropathy (orthostatic hypotension, gastroparesis, gustatory sweating) were more frequent (7/8 vs 10/27 patients). The mean QTc interval was not different between the groups. These results suggest a relatively poor prognosis of patients with CADN in the absence of clinically detectable micro‐ and macrovascular complications.