bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Myocardial Infarction in Diabetic Patients in the Thrombolytic Era
Authors: Lynch M. , Gammage M.D. , Lamb P. , Nattrass M. , Pentecost B.L.
Published: July 2009

To examine the benefits of thrombolytic therapy in diabetic patients with acute myocardial infarction a retrospective study of all diabetic and non‐diabetic patients with acute myocardial infarction admitted to the coronary care unit of the General Hospital, Birmingham between January 1984 and December 1987 was made and findings compared to corresponding groups admitted between January 1990 and May 1992 when thrombolytic therapy was routine. In‐hospital mortality and morbidity were assessed in 208 diabetic and 1029 non‐diabetic patients with acute myocardial infraction admitted between 1984 and 1987 and in 115 diabetic and 501 non‐diabetic patients admitted with myocardial infarction between January 1990 and May 1992. Following the introduction of thrombolytic therapy, there was a reduction in mortality among non‐diabetic patients from 17 % to 8.5 %; p± 0.001 (observed reduction: 49 %; 95 % Cl: 30–70 %) and in the incidence of left ventricular failure (from 22 % to 8 %, p ± 0.01 (observed reduction: 52 %; 95 % Cl: 40–85.5 %). Diabetic patients showed a reduction in mortality from 30 % to 17 %; p = 0.02 (observed reduction: 42 %; 95 % Cl: 9.4–73.8 %) and in the incidence of left ventricular failure from 39 % to 21 %; p ± 0.01 (observed reduction: 45 %; 95 % Cl: 20.3–72.5 %). Thrombolytic therapy confers a major benefit on diabetic patients with acute myocardial infarction, although this group remains at a prognostic disadvantage compared to non‐diabetic patients.
Prevalence of Islet Cell and Thyrogastric Autoantibodies in Sudanese Patients with Type 1 Diabetes
Authors: Magzoub M.M.A. , Abdel‐Hameed A.A. , Bottazzo G.F.
Published: July 2009

In this study, sera from 96 Sudanese patients with Type 1 diabetes and from 86 matched controls were tested for the following organ‐specific antibodies: islet cell antibodies (ICA), thyroid microsomal antibodies (TMA), antithyroglobulin antibodies (ATA), and gastric parietal cell antibodies (PCA). In diabetic patients the prevalence rates of these antibodies were: ICA = 41.7 %, ATA = 2.0 %, TMA = 7.3 %, PCA = 6.3 %. All these rates were significantly higher than in controls except for ATA which showed similar low prevalence rates in patients and controls. The pattern of prevalence of these antibodies by age, sex, and duration of diabetes was assessed and compared with reports from other populations. The general pattern of these antibodies is similar to that reported in Caucasian populations, except for a slightly greater tendency for ICA to persist with increased duration of diabetes in our sample. Furthermore, the low prevalence of TMA in our population is comparable to that reported in Black American diabetic patients but significantly lower than rates reported in certain other racial groups.
UK Prospective Diabetes Study (UKPDS) XI: Biochemical Risk Factors in Type 2 Diabetic Patients at Diagnosis Compared with Age‐matched Normal Subjects
Authors:   UK Prospective Diabetes Study Group
Published: July 2009

A total of 507, newly diagnosed, white Caucasian Type 2 diabetic patients entered into UK Prospective Diabetes Study, mean age 52±9 (SD) years have been compared with 195 age‐matched normal subjects (fasting plasma glucose<6 mmol l‐1) who had no known first degree relatives with diabetes. Diabetic patients were more obese BMI(kg m‐2) 30.1 ± 6.2 vs 26.2 ± 4.0, respectively, with female (F) diabetic patients more so than male (M). Fasting plasma glucose (mmol l‐1) was 12.2 ± 3.8 vs 5.0 ± 0.6 in diabetic and normal subjects, and, haemoglobin A1c(%) 9.3 ± 2.3 vs 5.4 ± 0.4. Hyperinsulinaemia (mU l‐1) was prevalent in both male and female diabetic patients, after adjustment for BMI (geometric mean 1SD interval, M 12.1 (11.8 to 12.4) vs 8.3(7.8 to 8.9) and F 13.3(12.9 to 13.7) vs 7.4 (7.1 to 7.7). Plasma triglyceride (mmol l‐1) was higher in diabetic patients, 1.8 (1.1 to 2.9) vs 1.1 (0.6 to 1.8). Total cholesterol (mmol l‐1) was slightly elevated in diabetic patients, with females in both populations higher than males, M 5.5 ± 1.2 vs 5.2 ± 0.9 and F 5.8 ± 1.1 vs 5.5 ± 1.1. HDL cholesterol (mmol l‐1) was slightly lower in male and markedly lower in female diabetic patients than in normal subjects, M 1.00 ± 0.26 vs 1.11 ± 0.22 and F 1.12 ± 0.27 vs 1.42 ± 0.33. Urine albumin was raised in diabetic patients (mg l‐1) 16.3 (5.2 to 50.9) vs 7.2 (3.2 to 16.5), as was urine N‐acetylglucosaminidase (U l‐1 6.4 (3.5 to 11.7) vs 2.9 (1.9 to 4.5) and plasma N‐acetylglucosaminidase (U l‐1) 11.5 ± 3.2 vs 10.2 ± 2.3. Normal subjects aged above 65 years, had slightly higher haemoglobin A1c, insulin, C‐peptide, plasma and LDL cholesterol, triglyceride, plasma and urine N‐acetylglucosaminidase and lower HDL cholesterol than younger subjects. The 2.5 and 97.5 percentiles for biochemical variables are presented for both populations aged 25—65 years.
A Search for Candidate Viruses in Type 1 Diabetic Pancreas Using the Polymerase Chain Reaction
Authors: Foy C. A. , Quirke P. , Williams D. J. , Lewis F. A. , Grant P. J. , Eglin R. , Bodansky H. J.
Published: July 2009

In order to investigate a possible viral aetiology for Type 1 diabetes the polymerase chain reaction (PCR) technique was used. Pancreatic tissue from Type 1 diabetic subjects was examined for the presence of a panel of common viruses. Primers specific for mumps, measles, cytomegalovirus, and Epstein Barr virus, as well as primers located in a highly conserved region of the enterovirus genome which are capable of detecting all of the following family members: Coxsackie B, echovirus, polio, mengovirus, and encephalomyocarditis virus were used to screen 18 Type 1 diabetic subjects of whom 3 had proven insulitis, 12 Type 2 diabetic subjects and 18 non‐diabetic controls. Epstein Barr virus was detected in two Type 1 (13%), two Type 2 (22%), and three of the normal non‐diabetic pancreases (20%), and the DNA sequences confirmed by direct sequencing. Cytomegalovirus was detected in one of the normal pancreases only and no evidence of any of the other viruses was found. It is concluded that the Type 1 diabetic pancreatic samples studied did not show persistence of infection with any of the above viruses. Non‐persistent acute infection of the pancreas by the above viruses cannot be excluded in the aetiology of Type 1 diabetes from this study.
Psychological and Demographic Correlates of Glycaemic Control in Adult Patients with Type 1 Diabetes
Authors: Hepburn D. A. , Langan S. J. , Deary I. J. , Macleod K. M. , Frier B. M.
Published: July 2009

The relationship between an objective measure of glycaemic control (glycated haemoglobin (HbA1)) and personality variables was examined in two separate groups of adult Type 1 (insulin‐dependent) diabetic patients. Study 1 included 121 patients, all of whom also had subjective self‐reporting of treatment compliance assessed, while the first 57 patients had individual differences in intelligence, major dimensions of personality and forgetfulness documented. Study 2 examined 303 patients, all of whom had their major dimensions of personality assessed using a shortened and updated version of the original personality questionnaire. Demographic indices (age, onset‐age, duration of diabetes) were assessed in both groups. No significant correlation was found between HbA1 and self‐report compliance suggesting that self‐reporting may be invalid as a measure of glycaemic control. In study 1 personality and intelligence variables did not correlate significantly with HbA1 values. Older patients with shorter duration of diabetes had significantly better glycaemic control (p<0.05). A significant correlation was observed between HbA1 concentration and onset‐age of diabetes (p<0.001); the patients who had developed diabetes later in life were achieving better control of their blood glucose. In the larger number of subjects in study 2 no significant correlations were evident between HbA1 and personality variables. It is concluded that the predictors of glycaemic control indexed by HbA1 may be distinct from predictors of self‐report compliance and that the latter have limited or no value in providing an assessment of quality of glycaemic control. There is no evidence of an effect of personality on glycaemic control as measured by HbA1.
Early Onset Diabetes: Parents' Views
Authors: Parker H. , Swift P. G. F. , Botha J. L. , Raymond N. T.
Published: July 2009

During 1990–91 postal questionnaires were sent to the parents of 309 children living in the United Kingdom who developed diabetes before the age of 2 years during 1972–1981. The aim of the survey was to explore how they had coped with their child's condition. Completed questionnaires were returned by 85% of parents. The children had a mean age of 14 (range 9–19) years and diabetes for a mean duration of 13 (range 9–18) years. The cohort's mean age for starting self‐injection was reported to be 8 years and most of the children (82%) were still attending full‐time education. Diabetes‐related difficulties at school were reported for 34% (95% C I 28–40) of the children and 70 (27%, 95% C I 22–32) were estimated to have missed more schooldays than their peers. With increasing duration of diabetes, parents expressed a reduction in anxiety about practical aspects of management such as injections and monitoring, but concern about hypoglycaemia and long‐term vascular complications remained high. Parents of girls were more likely to express worries compared to parents of boys, and this excess was significant for worry about diet (χ21df = 17.021, p < 0.001). The paediatric diabetes team caring for early diagnosed children should be aware of the need to discuss the long‐term implications of the disorder and be sensitive to the transition period when the child takes progressively more responsibility for self management and the parent's role diminishes.
The Prospective Assessment of Autonomic Nerve Function by Pupillometry in Adolescents with Type 1 Diabetes Mellitus
Authors: Donaghue Kim C. , Pena M.M. , Fung A.T.W. , Bonney M. , Howard N.J. , Silink M. , Schwingshandl J.
Published: July 2009

The study aimed to compare the longitudinal assessment of autonomic nerve function by computerized infrared pupillometry and standard cardiovascular tests in adolescents with diabetes. Adolescents (n = 150) were assessed at two time points (T1 and T2). The median time interval between assessments was 1.5 (range 0.9–3) years. At T1 the median age was 14.5 (range 8.3–19.5) years and the median duration was 6.5 (range 1.1–16) years. The pupillary variables assessed included the resting pupil diameter, the maximum constriction velocity, and the reflex amplitude of constriction. Heart rate reflexes were assessed in response to deep breathing, the Valsalva manoeuvre, and on standing from a lying position (30/15 ratio). Between visits there was a significant decrease in maximum constriction velocity (6.0 mm s−1 vs 6.3 mm s−1, p = 0.0001) and resting pupil diameter (6.2 mm vs 6.3 mm, p = 0.001). At reassessment pupillary abnormalities increased from 32 (21 %) to 45 (30%), with 17 (54 %) of the initial abnormalities persisting. Adolescents with abnormally slow maximum constriction velocity compared to those with normal maximum constriction velocity had a higher glycated haemoglobin (HbA1c%) at T2 (p = 0.02) and between assessments (p = 0.01). Cardiovascular test abnormalities did not increase between visits and the persistence of initial abnormalities was low (21 %). In summary, pupillometry appears a more sensitive test of autonomic nerve dysfunction in adolescents with diabetes than assessment of cardiovascular reflexes.
Peripheral Osteopenia in Adult Patients with Insulin‐dependent Diabetes Mellitus
Authors: Forst T. , Beyer J. , Pfützner A. , Kann P. , Schehler B. , Lobmann R. , Schäfer H. , Andreas J. , Bockisch A.
Published: July 2009

Alterations in bone metabolism in diabetes mellitus is a topic of special interest. Bone blood flow is increased in the distal limb of diabetic patients, which is believed to increase osteoclastic activity. We measured bone mineral density using dual‐photon absorptiometry in the distal lower limb, the femoral neck, and the lumbar spine in 41 IDDM patients and in 30 control persons, In the diabetic group there was a 10 % reduction of bone mineral density in the femoral neck (p < 0.01) and a 12 % reduction in the distal limb (p < 0.001) compared with the control group. No significant difference was found in the lumbar spine (p = 0.22). Our data yield incidence for peripheral osteopenia in IDDM‐patients, independent of any systemic bone diseases such as osteoporosis. A link between decreased bone mineral density and diabetic neuropathy has been observed for the femoral neck (p < 0.001), but not for the distal limb or axial skeleton. Whether there is a common aetiological link or a causal connection between diabetic neuropathy and bone mineral density has still to be determined.
Mortality and Morbidity in Treated Hypertensive Type 2 Diabetic Patients with Micro‐ or Macroproteinuria
Authors: Sawicki P.T. , Mühlhauser I. , Didjurgeit U. , Reimann M. , Bender R. , Berger M.
Published: July 2009

In order to describe the natural history of high risk diabetic patients treated for hypertension we have followed a sequential sample of 100 hypertensive Type 2 diabetic patients with elevated urinary protein excretion (≥60 mg 24 h−1) for a period of 1–7 years. Antihypertensive treatment was instituted in all patients and, in addition, the patients were offered the possibility of participation in an intensified antihypertensive therapy programme. After a mean follow‐up of 4 years overall mortality was 13 %. Nineteen percent of all patients experienced a cardiovascular event and 7 % a cerebrovascular event. In conclusion, in this study the overall mortality was lower that previously reported in proteinuric Type 2 diabetic patients. Antihypertensive treatment may account for this outcome.
Effects of Age and Obesity on Glycated Haemoglobin and 1,5‐anhydroglucitol in Screening for Type 2 Diabetes Mellitus
Authors: Tsukui S. , Kobayashi I.
Published: July 2009

The diagnostic accuracy of glycated haemoglobin (HbA1c) and 1,5‐anhydroglucitol (AG) and their association with age and obesity in the community screening for Type 2 diabetes were investigated. HbA1c and AG were measured in 368 subjects at the time of an oral glucose tolerance test (OGTT) based on WHO criteria. The impact of age and obesity on the probability of diabetes was evaluated by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to assess diagnostic accuracy of each method. The areas under ROC curves were compared for subjects aged 30–59 and 60–82 years. In the logistic analysis, age was associated with the probability of diabetes, while body mass index did not contribute to the model. The paired ROC analyses indicated that HbA1c was superior to AG only in the younger subjects. When the areas for two age groups were compared, both HbA1c and AG performed better in the younger than older subjects. We conclude that for the younger subjects, HbA1c value is highly sensitive (100.0 %) and specific (90.4 %), and is helpful for the diagnosis of Type 2 diabetes. On the other hand for the older subjects, both HbA1c and AG are poor screening tests in reference to the OGTT standard.
The Influence of Insulin Antibodies on the Pharmacokinetics of NPH Insulin in Patients with Type 1 Diabetes treated with Human Insulin
Authors: Peters A. , Kerner W. , Klose O. , Hefty R. , Keck F.
Published: July 2009

The influence of insulin binding antibodies on the pharmacokinetics of NPH insulin was studied in Type 1 diabetic patients on human insulin. Insulin‐antibody binding (Bo) was measured during a screening procedure in 155 Type 1 diabetic patients. In 36 patients, Bo was <1.5%, and in 38 patients Bo was >10.0%. Of these, 6 patients, group 1 (Bo < 1.5%) and 8 patients, group 2 (Bo > 10.0%), respectively, subsequently participated in a pharmacokinetic study. Free insulin and the glucose infusion rate were measured using a euglycaemic clamp after subcutaneous injection of NPH insulin (0.4 U kg−1). The areas under the curve (AUC) of free insulin concentration were smaller for group 2 (p = 0.01) than for group 1 (212.2 ± 22.0 vs 316.8 ± 25.3 mU l−1 h). The AUCs of the glucose infusion rate were also smaller for group 2 (p < 0.05) than for group 1 (2.50 ± 0.32 vs 3.58 ± 0.36 g kg−1). A significant negative correlation exists between the AUCs for free insulin concentration and insulin‐antibody binding Bo (r=0.76, p = 0.001). The daily insulin dosage was higher in group 2 (p = 0.02) than in group 1 (0.66 ± 0.03 vs 0.53 ± 0.03 U kg−1). We conclude that insulin antibodies influence the pharmacokinetics of NPH human insulin. The demonstrable influence on the kinetics of free insulin and glucose utilization leads to a slight increase in daily total insulin requirements.
BOOK REVIEW
Authors: Bain S.C.
Published: July 2009

Book reviewed in this article:

Molecular Biology of Diabetes, part 1: Autoimmunity and Genetics; Insulin Synthesis and Secretion edited by B. Draznin and D. LeRoith
Development and Progression of Diabetic Retinopathy: Adolescents at Risk
Authors: Bonney M. , Hing S.J. , Fung A.T.W. , Stephens M.M. , Fairchild J.M. , Donaghue K.C. , Howard N.J. , Silink M.
Published: July 2009

The aims of this study were to evaluate short‐term changes in retinopathy in adolescents, and to examine the relationship of these changes to risk factors. Two‐hundred and three adolescents, with a median age of 14.5 (range 10.4 to 20.6) yr and a median duration of diabetes of 6.6 (1.1 to 16.3) yr, were included in the study. Retinopathy was assessed on two occasions, using stereoscopic fundus photography; the median time between assessment was 1.3 (0.5 to 3.0) yr. At baseline, 41 % of the adolescents had background retinopathy. When patients were stratified according to the median diabetes duration (DD) (6.6 yr) and glycaemic control over the 12 months prior to assessment (HbA1c) (8.4 %), the percentage of retinopathy in each group was: lowDD/lowHbA1c 13 %; lowDD/highHbA1c 40 %; highDD/lowHbA1c 42 %; and highDD/highHbA1c 72 %. Using a 2‐step criteria for stability or change in retinopathy, 11 % of the 203 adolescents showed progression of retinopathy, 41 % had stable retinopathy, 5 % showed regression, and 43 % had no retinopathy at either assessment. Change in retinopathy was related to age at baseline assessment (borderline significance, p = 0.06), diabetes duration (p < 0.001), glycaemic control (p < 0.001) and total cholesterol (p = 0.04), and was also related to DD/HbA1c group membership (X2p < 0.001). This study highlights the combined adverse effect of long diabetes duration and poor glycaemic control on the development and progression of retinopathy during adolescence, and identifies a group that is likely to show progression over a relatively short period.
Detection of Common Viruses Using the Polymerase Chain Reaction to Assess Levels of Viral Presence in Type 1 (Insulin‐dependent) Diabetic Patients
Authors: Foy C.A. , Quirke P. , Lewis F.A. , Futers T.S. , Bodansky H.J.
Published: July 2009

The polymerase chain reaction was used to detect a range of common viruses in the peripheral blood of Type 1 diabetic and non‐diabetic control patients in order to identify any abnormal viral presence, with possible roles in the pathogenesis of Type 1 diabetes. Peripheral blood from 17 newly diagnosed Type 1 diabetic patients, 38 Type 1 diabetic patients with disease of longer duration, and 43 age and sex matched non‐diabetic controls was obtained. Samples were screened for cytomegalovirus, Epstein‐Barr virus, enterovirus (including coxsackie), and mumps virus. Cytomegalovirus was detected in control patients only (5 %), Epstein‐Barr virus was detected equally in newly diagnosed and control patients (12%), and enterovirus was detected slightly more frequently in diabetic than non‐diabetic patients (41% and 31%, respectively). Mumps virus was not detected in any of the samples. It is concluded that Type 1 diabetic individuals are neither more prone to persistence of common viruses nor to more frequent acute infections with the viruses tested for than non‐diabetic individuals. If common viruses are involved in the pathogenesis of Type 1 diabetes then they act either as non‐specific agents to which the host has abnormal immune responses, or, the diabetogenic viruses are eliminated from the body by the time of disease diagnosis.
Islet Cell Antibodies and Beta‐cell Function in Gestational Diabetic Women: Comparison to First‐degree Relatives of Type 1 (Insulin‐dependent) Diabetic Subjects
Authors: Mauricio D. , Corcoy R. , Codina M. , Morales J. , Balsells M. , de Leiva A.
Published: July 2009

In order to further characterize women with islet cell antibodies (ICA) at the diagnosis of gestational diabetes (GDM), we aimed to compare titres and persistence as well as B‐cell function with those of ICA+ first‐degree relatives of Type 1 (insulin‐dependent) diabetic subjects. Titres at detection of ICA were compared between 69 women with GDM and 53 relatives. Persistence of ICA positivity was investigated in 33 ICA+ gestational diabetic women and 39 relatives (mean follow‐up: 13 months). Assessment of the acute insulin response, through an intravenous glucose tolerance test (IVGTT), was carried out in 9 ICA+ women with previous GDM and normal oral glucose tolerance, and their results were compared to those of a control group (9 women) and a group of 12 adult ICA+ relatives. In comparison with first‐degree relatives, women with GDM had a higher ICA prevalence, especially with titres of <20 JDF, and a similar persistence at follow‐up. Women with ICA at diagnosis of GDM and normal oral glucose tolerance after pregnancy showed a decreased insulin response to glucose as compared to the control group. Results of the IVGTT closely paralleled those from adult ICA+ relatives. It is concluded that ICA+ gestational diabetic women share with ICA+ first‐degree relatives of Type 1 diabetic subjects metabolic and immunologic disturbances.
Nephropathy in Type 1 Diabetes: the Role of Genetic Factors
Authors: Chowdhury T. A. , Kumar S. , Barnett A. H. , Bain S. C.
Published: July 2009

Diabetic nephropathy affects up to 30% of all patients with Type 1 (insulin‐dependent) diabetes and is associated with a high morbidity and mortality. A number of studies have suggested that, unlike retinopathy or neuropathy, the influence of hereditary factors on the development of nephropathy is strong. Much interest has focused on possible genetic markers indicating an increased risk for developing diabetic nephropathy. It is envisaged that patients with Type 1 diabetes may be screened at diagnosis for increased susceptibility to nephropathy and subsequently have intensified follow up and possibly even prophylactic therapy in order to prevent progression to nephropathy. Two groups of candidate genes have so far been of particular interest: those implicated in the aetiology of hypertension, and those involved in the metabolism of glomerular basement membrane proteins. This article aims to review the evidence suggesting a role for hereditary factors, possible genetic models, and the genetic loci thought to be involved.
Counting the Cost of Diabetic Hospital Admissions from a Multi‐ethnic Population in Trinidad
Authors: Gulliford M. C. , Ariyanayagam‐Baksh S. M. , Bickram L. , Picou D. , Mahabir D.
Published: July 2009

Many middle‐income countries are experiencing an increase in diabetes mellitus but patterns of morbidity and resource use from diabetes in developing countries have not been well described. We evaluated hospital admission with diabetes among different ethnic groups in Trinidad. We compiled a register of all patients with diabetes admitted to adult medical, general surgical, and ophthalmology wards at Port of Spain Hospital, Trinidad. During 26 weeks, 1447 patients with diabetes had 1722 admissions. Annual admission rates, standardized to the World Population, for the catchment population aged 30–64 years were 1031 (95% CI 928 to 1134) per 100 000 in men and 1354 (1240 to 1468) per 100 000 in women. Compared with the total population, admission rates were 33% higher in the Indian origin population and 47% lower in those of mixed ethnicity. The age‐standardized rate of amputation with diabetes in the general population aged 30–64 years was 54 (37 to 71) per 100 000. The hospital admission fatality rate was 8.9% (95% CI 7.6% to 10.2%). Mortality was associated with increasing age, admission with hyperglycaemia, elevated serum creatinine, cardiac failure or stroke and with lower‐limb amputation during admission. Diabetes accounted for 13.6% of hospital admissions and 23% of hospital bed occupancy. Admissions associated with disorders of blood glucose control or foot problems accounted for 52% of diabetic hospital bed occupancy. The annual cost of admissions with diabetes was conservatively estimated at TT$ 10.66 million (UK£1.24 million). In this community diabetes admission rates were high and varied according to the prevalence of diabetes. Admissions, fatalities and resource use were associated with acute and chronic complications of diabetes. Investing in better quality preventive clinical care for diabetes might provide an economically advantageous policy for countries like Trinidad and Tobago.
The Effect of Acute (60 minute) Insulin Stimulation upon Human Skeletal Muscle Glycogen Synthase and Protein Phosphatase‐1 in Non‐insulin‐dependent Diabetic Patients and Control Subjects
Authors: Barriocanal L. A. , Borthwick A. C. , Stewart M. , Wells A. , Hurel S. J. , Yeaman S. J. , Taylor . R.
Published: July 2009

Previous studies have established that activation of muscle glycogen synthase (GS) is abnormal in non‐insulin‐dependent diabetes mellitus (NIDDM). Insulin‐mediated activation of GS depends upon protein phosphatase‐1 (PP1), which dephosphorylates the relevant sites of GS. In order to determine whether defects in PP1 activation cause subnormal activation of GS or whether PP1 activation itself is normal, we administered a short insulin infusion to 8 NIDDM subjects and 8 healthy controls matched for gender, age, and body mass index (BMI). GS fractional activity and PP1 activity were determined in biopsies taken from the gastrocnemius muscle before and after 60 min insulin infusion (0.1 U kg h−1). In the NIDDM group, muscle GS fractional activity was 6.8 ± 1.6 and 10.0 ± 1.5% (mean ± SEM) (p = 0.11) before and after insulin infusion. In the control group, muscle GS fractional activity increased from 7.3 ± 2.0 to 13.3 ± 2.7% (p < 0.02). PP1 activity had returned towards basal levels after insulin infusion; NIDDM group 156 ± 24.7 to 184.1 ± 28.1 U mg−1; control group 220.8 ± 30.1 to 233.8 ± 29.8 U mg−1. In the NIDDM group there was a positive correlation between the increases in GS fractional activity and PP1 activity following insulin stimulation r = 0.77; p < 0.025). These data indicate that in vivo insulin‐dependent activation of muscle PP1 is transient in normal subjects but is delayed in NIDDM. The defect in GS activation in NIDDM is likely to be proximal to PP1 in the pathway of transmission of the insulin signal.
Maternally Inherited Diabetes Mellitus: the Role of Mitochondrial DNA Defects
Authors: Alcolado J.C. , Thomas A.W.
Published: July 2009

Several studies have shown a consistent maternal effect in the transmission of Type 2 diabetes (NIDDM). The mitochondrial encephalomyopathies are a group of diseases characterized by maternal inheritance and a variety of mitochondrial DNA defects. Diabetes is a feature of some of these disorders and therefore the hypothesis arose that mitochondrial DNA mutations might play a role in patients with diabetes but no other features of neurological disease. Recent studies have confirmed that a specific point mutation in the gene encoding the mitochondrial tRNA for leucine segregates with diabetes and nerve deafness in families from the UK, Holland, France and Japan. Mitochondrial gene deletions have also been reported. Affected subjects present with progressive insulin deficiency and may fall into the broad classifications of either Type 1 (IDDM) or Type 2 diabetes (NIDDM). Future studies are aimed at searching for other mitochondrial gene defects in diabetes and attempting to explain the mechanism of hyperglycaemia by the development of phenotypic expression systems. Although an exciting development in the genetics of diabetes, currently described mitochondrial mutations do not fully explain the maternal effect in the transmission of Type 2 diabetes.
Topical Treatment of Diabetic Foot Ulcers: an Economic Analysis of Treatment Alternatives and Strategies
Authors: Apelqvist J. , Ragnarson‐Tennvall G. , Larsson J.
Published: July 2009

In a prospective study, 314 patients with diabetic foot ulcers were followed and 40 patients died before healing occurred. In those patients who healed, a retrospective economic analysis of the costs for topical treatment was performed. The aim of the study was to analyse the costs and discuss how different treatment strategies influence total costs. Data collected for each patient were total time to healing, treatment time for each type of dressing, and the frequency of dressing changes. Material costs for the dressings, labour, and travelling costs were calculated separately. A formula for simulation of economic consequences of different treatment strategies including the introduction of new strategies was designed. The cost for topical treatment was strongly related to the severity of the ulcer and wound healing time. The average weekly cost per patient for topical treatment varied between £40.3 and £385. The dominating costs for topical treatment were expenses for staff and transportation. The most important factor to reduce costs is the frequency of dressing changes. The study emphasizes the need for prospective comparative studies of cost effectiveness in topical treatment strategies.
Proteinuria and Mortality in Diabetes: the WHO Multinational Study of Vascular Disease in Diabetes
Authors: Stephenson J.M. , Kenny S. , Stevens L.K. , Fuller J.H. , Lee E. ,   WHO Multinational Study Group
Published: July 2009

The relation between proteinuria and mortality was investigated in 1188 patients with Type 1 diabetes and 3234 patients with Type 2 diabetes, aged 35–55 at baseline and followed up for a mean of 9.4 ± 3.1 years in the WHO Multinational Study of Vascular Disease in Diabetes. Baseline prevalence of light or heavy proteinuria was the same (25%) in both types of diabetes after adjustment for differences in diabetes duration. Compared with patients with no proteinuria, all cause mortality ratios were 1.5 (95% confidence interval 1.1–2.0) and 2.9 (2.2–3.8) for Type 1 patients with light and heavy proteinuria, respectively, and 1.5 (1.2–1.8) and 2.8 (2.3–3.4) for Type 2 patients, after adjustment for age, duration of diabetes, blood pressure, cholesterol, and smoking. Proteinuria was associated with significantly increased mortality from renal failure, cardiovascular disease, and all other causes of death. In both types of diabetes, the association was strongest for renal deaths, and of similar magnitude for cardiovascular and all other causes of death. In conclusion, proteinuria is a common, important, and rather non‐specific risk factor for increased morbidity and mortality in diabetes. The relation of proteinuria to mortality is similar for both types of diabetes. The benefits and risks of proteinuria reduction should be examined in large randomized trials with clinical endpoints.
Whole‐body Glucose Metabolism in Obese Patients with Type 2 Diabetes Mellitus: the Impact of Hypertension and Strict Blood Glucose Control
Authors: Vestergaard H. , Parving H.H. , Hansen L. , Pedersen O.
Published: July 2009

We have examined the impact of hypertension and blood glucose control on insulin sensitivity in obese Type 2 (non‐insulin‐dependent) diabetic patients. Glucose metabolism in the basal state and in response to insulin was examined using the euglycaemic, hyperinsulinaemic (2 mU kg−1 min−1) clamp technique in combination with 3‐[3H]‐glucose infusion and indirect calorimetry in 60 obese Type 2 diabetic patients (30 normotensive patients and 30 hypertensive patients on antihypertensive treatment) and 10 obese normotensive control subjects. In the basal state and during hyperinsulinaemia, glucose disposal rates (total, oxidative, and nonoxidative) were similar in Type 2 diabetic patients with or without hypertension (230 ± 83 vs 270 ± 114 mg m−2min−1 (NS), 83 ± 28 vs 95 ± 7 mg m−2 min−1 (NS), 148 ± 70 vs 180 ± 89 mg m−2 min−1 (NS), treated hypertensive vs normotensive subjects, respectively). However, compared to obese control subjects (403 ± 65 mg m−2 min−1) both groups of diabetic patients had significantly decreased insulin‐stimulated glucose disposal rates (p < 0.005). Even in a subset of Type 2 diabetic patients with long‐term (> 6 months) near normal blood glucose control (HbA1c < 6.1 %) significant defects were detectable in whole‐body glucose and lipid metabolism when compared to control subjects. These results indicate that treated hypertension does not significantly aggravate the insulin insensitivity that is already present in Type 2 diabeted mellitus. Furthermore, Type 2 diabetic patients with long‐term good metabolic control continue to demonstrate insulin insensitivity in peripheral tissues.
One‐year Acarbose Treatment Raises Fasting Serum Acetate in Diabetic Patients
Authors: Wolever T.M.S. , Radmard R. , Chiasson J.‐L. , Hunt J.A. , Josse R.G. , Palmason C. , Rodger N.W. , Ross S.A. , Ryan E.A. , Tan M.H.
Published: July 2009

α‐Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1‐year, double‐blind, placebo‐controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 ± 5 vs 71 ± 4 μmol l−1) or glycosylated haemoglobin (HbA1c; 7.2 ± 0.3 vs 7.4 ± 0.3 %). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 ±4 vs 2 ± 3 μmol l−1 (p < 0.02) and reduced HbA1c by −0.59 ± 0.16 vs −0.13 ± 0.20 % (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non‐esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1c, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1‐year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side‐effects or changes in blood glucose control or serum lipids.
Postural Hypotension in Diabetic Autonomic Neuropathy: a Review
Authors: Purewal T.S. , Watkins P.J.
Published: July 2009

Postural hypotension is uncommon in diabetes but can occur secondary to autonomic neuropathy. Symptoms are rare and include dizziness, weakness, blurred vision, tiredness, and loss of consciousness. The pathophysiology of postural hypotension is not clear, but changes in intravascular volume, heart rate, cardiac output, and splanchnic vascular resistance are similar in patients and controls. The main factors producing hypotension are a blunted catecholamine response to standing, and failure of lower limb vascular resistance to increase adequately. Treatment for symptomatic postural hypotension includes avoidance of dehydration, adequate salt intake, and fludrocortisone. Other treatments are reviewed but are less helpful. Patients with postural hypotension have intermittent symptoms over the years but rarely become severely disabled. They have a poorer prognosis than patients with symptomatic autonomic neuropathy without postural hypotension.
Implementation of Intensified Insulin Therapy: a European Perspective
Authors: Berger Michael , Mühlhauser I.
Published: July 2009

The Diabetes Education Study Group (DESG) of the European Association for the Study of Diabetes (EASD) was founded in 1979 with its major goal to make effective patient training an integral part of any diabetes therapy. Within the DESG, a number of models for structured diabetes treatment and teaching programmes were developed. Concerning the care of persons with Type 1 diabetes, substantial emphasis was placed upon the 5‐day in‐patient treatment and teaching programme for groups of 6 to 10 patients as originally introduced at the University of Geneva and further developed for general use at the University of Düsseldorf. During the early 1980s, this programme was based upon intensified insulin therapy including a stepwise liberalization of previously rigid rules for nutrition and life schedules. In several European centres the programme was continuously evaluated and shown to be effective as documented by significant reductions of glycated haemoglobin values, episodes of ketoacidosis, hospitalizations, and sick‐day leaves. In contrast to the Diabetes Control and Complications Trial (DCCT) the improvement of glycated haemoglobin values was not associated with an increased risk of severe hypoglycaemia. Possible reasons for this favourable outcome are discussed. During recent years the 5‐day treatment and teaching programme for Type 1 diabetes has been translated into the general health care system of Germany without any loss of its efficacy. In addition, in various other European countries, model centres of diabetes care have implemented the 5‐day programme, and for a number of these centres, its efficacy to improve the overall quality of diabetes care has been published or presented at meetings.
Clinical Characteristics of Subjects with a Missense Mutation in Glucokinase
Authors: Page R.C.L. , Levy J.C. , Barrow B. , Turner R.C. , Patel P. , Hattersley A.T. , Lo D. , Wainscoat J.S. , Permutt M.A. , Bell G.I.
Published: July 2009

The clinical characteristics of subjects with a missense glucokinase mutation, gly299→arg, were studied in a large pedigree, BX, initially characterized by some members having Maturity Onset Diabetes of the Young (MODY). Glucose tolerance, beta cell function and insulin sensitivity were measured with Homeostasis Model Assessment (HOMA) and with a ‘Continuous Infusion of Glucose with Model Assessment’ (CIGMA) test. Diabetic complications were clinically assessed. Subjects with glucokinase gly299→arg were the same age, height, and obesity as the subjects without the mutation. Diabetes was usually asymptomatic at diagnosis and was treated with diet alone in 15 of the 18 subjects. Five of the 11 adult females had been diagnosed when they developed gestational diabetes. The fasting plasma glucose concentrations at the time of study were 4.3–12.6 mmol I−1, with the higher levels being in the more obese (p < 0.05) and in the older subjects (p < 0.05). In subjects with the mutation, beta cell function was impaired, being geometric mean 63% (normal‐100%) compared with 126% in the subjects without the mutation (p < 0.001) measured by HOMA and in a subset assessed by CIGMA 59% and 127% (p < 0.01), respectively. There was no difference in fasting insulin concentrations, insulin sensitivity, lipid concentrations or blood pressure between the groups. The haemoglobin A1c was raised (mean 6.5% compared with 5.5% in the subjects without the mutation), but microvascular and macrovascular complications were uncommon. The subjects with the mutation did not have microalbuminuria but had an impaired vibration perception threshold compared with subjects without the mutation. Subjects with the glucokinase missense mutation, gly299→arg had mild fasting hyperglycaemia commensurate with approximately a 50% decreased beta‐cell funtion. Longevity with few diabetic or vascular complications in members with the mutation may reflect the moderate hyperglycaemia and lack of dyslipidaemia and hypertension.
Day‐to‐day Variation of Insulin Sensitivity in Patients with Type 1 Diabetes: Role of Gender and Menstrual Cycle
Authors: Moberg E. , Kollind M. , Lins P‐E. , Adamson U.
Published: July 2009

The aim of the present study was to compare the day‐to‐day variations of the insulin sensitivity in male and female Type 1 diabetic patients and to assess the insulin sensitivity in the follicular and luteal phases of the menstrual cycle. Ten male and 20 female Type 1 diabetic patients participated in the study. The insulin sensitivity was assessed by the insulin (0.4 mU kg−1min−1)‐glucose/(4.5 mg kg−1min−1)‐infusion test (IGIT). In 5 of the female patients, a simultaneous i.v. influsion of somatostatin (100 μgh−1) was given (SIGIT). Each patient was studied twice, with 2 weeks separating the two tests. The day‐to‐day variations of the insulin sensitivity were almost identical in the male and female patients, the coefficients of variation being 13% in both groups. In 15 of the female patients, ovulation occurred. In these women, the mean blood‐glucose levels between 120 and 240 min after the onset of the IGIT/SIGIT were 9.8 ± 1.1 mmol l−1 in the follicular phase and 10.3 ± 1.0 mmol l−1 in the luteal phase, n.s. (95% confidence interval for the difference (luteal‐follicular) −0.8–1.9 mmol l−1). Although the present study cannot exclude minor changes of insulin sensitivity during the menstrual cycle, our results suggest that the changes of the metabolic control during the menstrual cycle, experienced by many women with Type 1 diabetes, are largely attributable to mechanisms other than variations of insulin sensitivity.
Decreased Urinary Dopamine Excretion and Disturbed Dopamine/Sodium Relationship in Type 1 Diabetes Mellitus
Authors: Segers O. , Gerlo E. , Dupont A.G. , Somers G.
Published: July 2009

In Type 1 diabetes an increased total body sodium and an impaired ability to excrete a sodium load have been described. A possible involvement of the renal dopaminergic system in this abnormal sodium handling was evaluated through measurements of the urinary output of dopamine, sodium, the dopamine/sodium correlation, and through examining the effect of a dopamine infusion on urinary sodium excretion. Twenty‐four hour urinary dopamine excretion was significantly lower in Type 1 diabetic patients as compared to normal controls. A significant correlation between urinary dopamine and sodium excretion was present in normoalbuminuric Type 1 diabetic patients and in normal controls. However, no such correlation could be found in microalbuminuric patients. The increase in fractional excretion of sodium during a 1 h low‐dose dopamine (3 μg kg−1min−1) infusion in Type 1 diabetic patients was negatively correlated with diabetes duration. Patients with short duration of diabetes (less than 15 years) had a comparable dopamine‐induced increase in fractional excretion of sodium as normal controls. However, patients with longer duration of diabetes (more than 15 years) and microalbuminuric patients displayed no significant changes in sodium output during dopamine infusion. These findings suggest that in Type 1 diabetes mellitus a deficiency of renal dopamine production could be responsible for the impaired sodium handling. Longer duration of the disease and microalbuminuria seem to be associated with an uncoupling of the urinary dopamine/sodium relationship.
Intranasal Insulin: the Effects of Three Dose Regimens on Postprandial Glycaemic Profiles in Type II Diabetic Subjects
Authors: Coates P.A. , Ismail I.S. , Luzio S.D. , Griffiths I. , Ollerton R.L. , Vølund A. , Owens D.R.
Published: July 2009

In both fasting normal and diabetic subjects, nasally administered insulin achieves significant falls in plasma glucose concentrations. Repeated administration before and during a meal has been necessary to lower postprandial glycaemic excursion in subjects with NIDDM. We have studied the use of Novolin® Nasal which employs a non‐irritant, lecithin‐based enhancer as a vehicle for human insulin, on postprandial glucose profiles in NIDDM subjects to determine efficacy, optimal dose frequency, and tolerability. Seventeen NIDDM subjects (15 men, 2 women) participated in a randomized, partially blinded, placebo‐controlled, crossover trial of three active treatment regimens (nasal insulin, 120 U at 0 min, 60 U at 0 and +20 min or 120 U at +20 min) in relation to a standardized mixed meal given at 0 min. All active treatments significantly reduced postprandial glucose concentrations compared to placebo. Intranasal insulin given at 0 min at a dose of 60 U or 120 U resulted in a 50% reduction in postprandial incremental glucose compared to placebo over the first 2 h, whereas treatment with 60 U both at 0 and 20 min lead to a 70% reduction over the 240 min postprandial period. Post‐prandial intravenous insulin was the least effective. There were no episodes of symptomatic hypoglycaemia. Local tolerability was excellent with only four reports of transient nasal irritation out of a total of 68 doses. The delivery device was accurate with intra‐device CV of delivered dose of 4.8%. We conclude that nasal insulin is effective in reducing postprandial glycaemia in subjects with NIDDM and is well tolerated. Repeated dosing achieved the greatest reduction in postprandial glycaemic responses to a mixed meal.
High Prevalence of Hepatitis C Infection in Afro‐Caribbean Patients with Type 2 Diabetes and Abnormal Liver Function Tests
Authors: Gray H. , Wreghitt T. , Stratton I.M. , Alexander G.J.M. , Turner R.C. , O'Rahilly S.
Published: July 2009

Moderate elevations of serum transaminases are frequently found in patients with diabetes mellitus and are often attributed to fatty infiltration of the liver without further investigation. Recent studies of patients with end‐stage liver disease have suggested a possible association between Hepatitis C virus (HCV) antibody positivity and the development of diabetes (mostly Type 2). As a first step in the examination of any potential association between HCV and Type 2 diabetes in subjects without overt liver disease, we examined 200 British patients with Type 2 diabetes (100 White Caucasians, 50 Asians, and 50 Afro‐Caribbeans), recruited from the United Kingdom Prospective Study of Diabetes, half of whom had a significant elevation of alanine aminotransferase (ALT) on at least two occasions and half of whom had consistently normal ALT levels. In Afro‐Caribbean Type 2 diabetic subjects 7/25 (28%) patients with abnormal ALT and 1/25 (4%) with normal ALT were HCV antibody positive. Among White Caucasian subjects 6/50 (12%) patients with abnormal LFTs and 0/50 with normal LFTs were HCV antibody positive and in Asians the prevalence was 2/25 (8%) and 0/25, respectively. This study suggests that persistent mild to moderate elevation of serum transaminases in a patient with Type 2 diabetes should not automatically be attributed to the metabolic disturbances of diabetes. Particularly in Afro‐Caribbean subjects, HCV infection is a major diagnostic consideration. The question of whether HCV infection itself may have a diabetogenic action is worthy of further investigation.