bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Therapy in Type 2 Diabetic Subjects Suppresses Plasminogen Activator Inhibitor (PAI‐1) Activity and Proinsulin‐like Molecules Independently of Glycaemic Control
Authors: Jain S.K. , Nagi D.K. , Slavin B.M. , Lumb P.J. , Yudkin J.S.
Published: July 2009

Eleven Type 2 diabetic subjects (10 male 1 female: age 56.2 ± 9.7 (SD) yr) were treated in random order either with insulin or with sulphonylureas for 8 weeks each, without attempting to alter glycaemic control between the two treatment periods. Insulin treatment was associated with suppression of endogenous insulin secretion (fasting C‐peptide levels ‐35.0 ± 24.2%; p = 0.006), and of intact proinsulin (‐43.1 ± 36.8%; p = 0.03) and 32,33 split proinsulin ‐20.1 ± 27.0%; p = 0.03). Activity of plasminogen activator inhibitor (PAI‐1), a fast acting inhibitor of fibrinolysis, decreased significantly (‐14.3% ± 27.5 %; p = 0.02) but no changes occurred in concentration of lipoproteins or apoproteins between therapies. Changes in concentrations of 32,33 split and intact proinsulin were closely and significantly related (rs = 0.83; p < 0.001) to each other but not with changes in concentrations of C‐peptide (intact proinsulin rs = ‐0.41; p = 0.11) and 32,33 split proinsulin rs = ‐0.27; (p = 0.21). Percentage changes in intact proinsulin concentrations were positively correlated with those in PAI‐1 (rs = 0.51; p = 0.05). There was, however a paradoxical negative relationship between changes in C‐peptide concentrations and those of PAI‐1 (rs = ‐0.73; p = 0.006). These preliminary observations suggest that insulin treatment in Type 2 diabetic subjects without any changes in glycaemic control is associated with a reduced activity of PAI‐1, but is without effect on any other cardiovascular risk factors. Concentrations of insulin precursor molecules may play a role in determining fibrinolytic activity.
Acute Effects of Local Hyperglycaemia on Peripheral Blood Flow in Man
Authors: Houben A.J.H.M. , Schaper N.C. , Kruseman A.C. Nieuwenhuijzen
Published: July 2009

To determine whether local hyperglycaemia affects peripheral blood flow in man, total forearm and skin microcirculatory blood flow were studied in healthy subjects before, during, and after a 1‐h infusion of different concentrations of glucose or mannitol in the brachial artery. Mild or high forearm hyperglycaemia, induced by 5% glucose infusion (≅ 10 mmol l‐1 and ≅ 18 mmol l‐1, respectively) did not induce any changes in forearm muscle or skin blood flow. However, mild forearm hyperglycaemia (≅ 8 mmol l‐1), induced by 20% glucose infusion, acutely increased forearm blood flow, decreased forearm vascular resistance, but did not change skin blood flow. Twenty percent Mannitol infusion, as an osmotic control, did not result in any changes. We conclude that intra‐arterial administration of 5% glucose does not acutely affect peripheral blood flow. The glucose‐related effect induced by 20% infusion is probably due to marked hyperglycaemia at the catheter tip.
Hypersecretion of Truncated Glucagon‐like Peptide‐1 and Gastric Inhibitory Polypeptide in Obese Patients
Authors: Fukase N. , Igarashi M. , Takahashi H. , Manaka H. , Yamatani K. , Daimon M. , Tominaga M. , Sasaki Hideo
Published: July 2009

Postprandial insulin secretion is modulated by both neural and humoral gastrointestinal insulinotropic factors in addition to the absorbed nutrient. To investigate the involvement of the potent insulinotropic hormones gastric inhibitory polypeptide (GIP) and truncated glucagon‐like peptide‐1 (tGLP‐1) in the postprandial hyperinsulinaemia of obesity, we examined the changes in plasma levels of GIP and tGLP‐1 by an oral glucose tolerance test (OGTT) in nine normal subjects (controls), nine obese subjects without glucose intolerance (Group A), and six obese mild diabetic patients (Group B). Following the OGTT, plasma GIP levels in Group B were increased more markedly than those in the other two groups. Plasma levels of tGLP‐1 were estimated by the difference between the values measured with the N‐terminal directed antiserum (GLP‐1NT) and those with the C‐terminal directed antiserum (GLP‐1 CT). Plasma levels of GLP‐1 NT were increased in Group B, but decreased in the other two groups. Plasma GLP‐1 CT levels were increased in all groups with the highest response in Group B. These results suggest that the combined augmentation of plasma GIP and tGLP‐1 responses were involved in the delayed and considerable increases in plasma insulin after glucose ingestion in obese diabetic patients. Since tGLP‐1 is suppressed in the hyperglycaemic hyperinsulinaemic state in normal subjects, the augmented tGLP‐1 response appears to be characteristic of obese Type 2 diabetes.
Sharing the Care of Diabetic Patients between Hospital and General Practitioners: Does it Work?
Authors: Hoskins P.L. , Fowler P.M. , Constantino M. , Forrest J. , Yue D.K. , Turtle J.R.
Published: July 2009

A randomized controlled trial was conducted to compare three forms of diabetes follow‐up: (1) general practitioner care, (2) a system of care shared between the general practitioner (GP) and clinic and (3) conventional clinic care. Two hundred and six diabetic patients without significant diabetes‐related or other medical complications were randomized to one of these follow‐up systems. Metabolic control and blood pressure improved significantly and equally in all three groups (p < 0.05). The shared care group performed as well as or better than either of the other two groups in all other outcome measures. In particular, final attendance rates were 72 % for shared care compared with only 35 % for GP care and 53 % for clinic care. Data collection rates for shared care were comparable with the clinic group for random blood glucose (88.9 % vs 95.1 %), weight (93.5 % vs 98.3 %), and blood pressure (94.8 % vs 92.7 %). Only in the case of glycosylated haemoglobin did shared care have poorer data collection (66.0 % vs 98.4 %). In all these parameters, except blood pressure, shared care out‐performed the GP group. We conclude that with adequate support from and communication with hospital‐based diabetes services, GPs are capable of providing care appropriate to the needs of uncomplicated diabetic patients.
A Prospective Study of Painful Symptoms, Small‐fibre Function and Peripheral Vascular Disease in Chronic Painful Diabetic Neuropathy
Authors: Benbow S.J. , Chan A.W. , Bowsher D. , MacFarlane I.A. , Williams G.
Published: July 2009

Fifty diabetic patients with chronic painful sensorimotor neuropathy were studied prospectively to clarify the natural history of this condition and the roles of small‐fibre damage and concomitant peripheral vascular disease (PVD). Initially, 30 patients had no significant PVD (ankle:brachial Doppler ratio > 1.0). Pain was assessed using a visual analogue scale (0–10 cm), and small‐fibre function by thermal limen (TL), heat‐pain threshold (HPT), and weighted pinprick threshold (PPT). At follow‐up, on average 3.6 years later (range 3.0–4.1), 11 patients had died (6 with PVD) and contact had been lost with 6. Pain scores fell in subjects without PVD (n = 24; median (range), from 4.8 (0.5–10.0) to 2.0 (0.0–9.2) cm, p < 0.001) and also in those with PVD (n = 9; from 5.1 (2.0–8.2) to 2.1 (0.0–8.0) cm, p < 0.05). Seven patients (5 without PVD) became pain‐free; at presentation, these 7 patients had experienced pain for a shorter period of time. Despite this symptomatic improvement, small‐fibre function generally deteriorated in both groups, with significant worsening (p < 0.05) of HPT and PPT in patients without PVD, and in HPT and TL in patients with PVD. Neuropathic pain therefore tends to improve with time and can resolve completely. By contrast, small‐fibre function continues to deteriorate, indicating that these peripheral measures do not predict the evolution of painful symptoms. The presence or absence of PVD does not appear to affect the natural history of neuropathic pain or its symptomatology.
Gender and the Clinical Usefulness of the Albumin:Creatinine Ratio
Authors: Connell S.J. , Hollis S. , Tieszen K.L. , McMurray J.R. , Dornan T.L.
Published: July 2009

One hundred and eighty‐seven diabetic and 105 control subjects collected timed overnight urine samples to measure the inter‐individual variation in creatinine excretion rate and its determinants, and to test the relationship between albumin excretion rate (AER) and two ‘surrogate measures’, the albumin concentration and albumin:creatinine ratio. Creatinine excretion was 55 % higher in men than women (geometric mean 8.9 μmol min−1 (95% confidence limits 4.7–17.0) compared with 5.7 (3.0–10.9); p < 0.001). Gender accounted for 31% of the variation in creatinine excretion and body mass index 1.4%; neither age nor the diabetic state had a significant effect. The relationships between AER and the two surrogate measures differed between diabetic subjects and controls such that relationships constructed from non‐diabetic data would not hold true for diabetes. Likewise, the relationship between AER and albumin:creatinine ratio differed between men and women such that a ratio of 4.0 mg mmol−1 corresponded to a predicted AER of 35 μg min−1 in men and 23 μg min−1 in women. The albumin:creatinine ratio outperformed albumin concentration in terms of sensitivity and specificity and its performance was better in women than men. We conclude that the albumin:creatinine ratio is a better surrogate for AER than albumin concentration. If ‘action levels’ are to be defined for screening programmes, they should be derived from diabetic and not non‐diabetic data and should be different in men and women. We propose a direct rather than screening role for the albumin:creatinine ratio in the management of diabetic nephropathy.
Higher Levels of Microproteinuria in Asian Compared with European Patients with Diabetes Mellitus and Their Relationship to Dietary Protein Intake and Diabetic Complications
Authors: Tindall H. , Martin P. , Nagi D. , Pinnock S. , Stickland M. , Davies J.A.
Published: July 2009

Asian patients with diabetes have a higher prevalence of renal disease than their European counterparts. The aim of the study was to investigate the pattern of the renal excretion of proteins in 70 Asian and 70 European patients with diabetes and to relate it to dietary intake of protein and prevalence of diabetic complications. Compared with matched Europeans, Asian patients had an increased urinary excretion of albumin and transferrin (p < 0.02) with 14 Asians and 6 Europeans having significant microalbuminuria (> 30 μg min−1). In 12 Asians and all 6 Europeans this was associated with complications from diabetes, particularly vascular. Asian patients had significantly more ischaemic heart disease (p < 0.001) but less neuropathy (p < 0.001) and retinopathy (p < 0.05) than their matched European counterparts. Asian diets were lower in protein (median (range) Asian vs European: 12.5% (6–29%) vs 19% (11–27%); p <0.01) and carbohydrate but higher in fat than European diets. There was no correlation between dietary protein intake and excretion of any of the urinary proteins measured. However, a significant correlation was found in Asians between protein intake and length of residence in the UK (p < 0.005). Unless ways to reduce complications can be found then future allocation of resources will need to take this into consideration in areas with large Asian communities.
Serum Insulin Level Versus Blood Pressure: A Cross‐sectional, Case‐controlled Study in Non‐obese, Middleaged Japanese Subjects with Normal Glucose Tolerance
Authors: Baba T. , Kodama T. , Tomiyama T. , Sohn D‐R , Ishizaki T.
Published: July 2009

To assess the relationship between blood pressure (BP) and serum insulin level in nonobese (body mass index (BMI) ≤ 27 kg m−2), middle‐aged (40–64 years of age) Japanese subjects with normal glucose tolerance, a three‐phase study protocol was designed. First, the responses of plasma glucose and serum insulin to an oral glucose load were compared between 40 patients with untreated essential hypertension and 40 age‐, sex‐ and BMI‐matched normotensive control subjects. Second, the glucose and insulin responses to an i.v. glucose load were evaluated in 7 non‐obese hypertensive, 7 non‐obese normotensive and 7 obese hypertensive subjects. Third, BP and serum lipid profile were compared between 21 hyperinsulinaemic (serum insulin level (while fasting, after glucose loading, or both) > 2 SDs higher than the mean) and 21 age‐, sex‐ and BMI‐matched normoinsulinaemic subjects (serum insulin level within 1 SD of the mean). The glucose and insulin responses to the oral glucose load were comparable between the hypertensive and normotensive groups. Similarly, the glucose and insulin responses to the i.v. glucose load were comparable between the non‐obese hypertensive and normotensive groups, whereas the mean AUCinsulin in the obese hypertensive group was significantly greater (p < 0.01) than that in either of the non‐obese groups. The respective mean values for systolic and diastolic BPs did not differ between the hyperinsulinaemic and normoinsulinaemic groups. The mean serum triglyceride and HDL cholesterol concentrations were significantly higher (p < 0.01) and lower (p < 0.05), respectively, in the hyperinsuslinaemic than in the normoinsulinaemic group. The results suggest no association between serum insulin level and BP in non‐obese, middle‐aged, Japanese subjects with normal glucose tolerance.
Fructosamine in Obese Normal Subjects and Type 2 Diabetes
Authors: Ardawi M.S.M. , Nasrat H.A.N. , Bahnassy A.A.
Published: July 2009

The effect of various grades of obesity on serum fructosamine concentrations was studied in Type 2 diabetic (n = 105) and non‐diabetic (n = 128) subjects. In obese diabetic and non‐diabetic subjects (body mass index ≥ 30 kg m−2), the concentration of fructosamine was markedly lower than that obtained for lean diabetic and non‐diabetic subjects with similar glycaemic control. Stepwise multiple‐regression analysis showed that fructosamine was associated with glycaemic control (as indicated by fasting plasma glucose and glycated haemoglobin), fasting triglycerides, and body mass index in both diabetic and non‐diabetic subjects. In vitro studies showed marked decreases in both the extent of [14C]‐glucose incorporation into plasma proteins and fructosamine production by incubated sera of obese patients whether diabetic or non‐diabetic, with obese subjects with body mass index > 40 kg m−2 exhibiting the greatest decrease. In conclusion, serum fructosamine concentrations are shown to decrease in obese diabetic and non‐diabetic subjects with body mass index ≥ 30 kg m−2 giving rise to the underestimation of glycaemic control as indicated by fructosamine measurement. A change in the glycation reaction itself may be partly responsible for such decrease.
Antibodies to Heat Shock Protein 65 kD in Type 1 Diabetes Mellitus
Authors: Tun R.Y.M. , Smith M.D. , Lo S.S.S. , Rook G.A.W. , Lydyard P. , Leslie R.D.G.
Published: July 2009

To determine whether antibodies to mycobacterial heat shock protein of 65 kD molecular weight (hsp 65) could be important in the pathogenesis of Type 1 diabetes we tested patients before and at diagnosis of diabetes, as well as patients with rheumatoid arthritis. Using ELISA, increased hsp 65 antibodies were detected in 2 of 8 pre‐diabetic twins, 1 of 13 newly diagnosed untreated diabetic patients and 3 of 10 rheumatoid arthritis patients. Levels of hsp 65 antibodies in pre‐diabetic twins, median (range), 0.25 (0.104–1.904) and newly diagnosed diabetic patients (mean ± SD) (0.299 ± 0.220), did not differ significantly either from each other or from their control subjects (0.134 ± 0.123). In contrast, levels of hsp 65 antibodies in rheumatoid patients (0.59 ± 0.42) were significantly higher than in their control subjects (0.21 ± 0.18; p = 0.02). Of twins studied prospectively before diagnosis, at diagnosis but before insulin treatment, and soon after diagnosis, three of four had hsp 65 antibodies at some stage. We conclude that serological immunity to mycobacterial hsp 65 can occur in Type 1 diabetes, but it is neither a characteristic nor a specific feature of the disease.
Modulation of Glucose and Growth Hormone Responses to Meals and Exercise in Type 1 Diabetes by Cholinergic Muscarinic Blockade
Authors: Ara J. , Kang S. , Creagh F.M. , Scanlon M.F. , Peters J.R.
Published: July 2009

Anticholinergic drugs suppress nocturnal and exercise‐related growth hormone (GH) secretion in Type 1 diabetes; nocturnal GH suppression is associated with a fall in fasting plasma glucose levels. The aim of this study was to assess the effect of GH suppression on glucose levels following a period of meals and exercise in physiological pattern. Six Type 1 diabetic men recruited from the outpatient clinic were studied in random order at least 1 week apart. After an overnight fast subjects received two‐thirds of their usual subcutaneous insulin and either 200 mg oral pirenzepine or placebo at time 0 min. Between 90 and 120 min subjects exercised continuously on an ergometric cycle. Standard meals or snacks were eaten at 30, 150, 270, and 390 min. Venous blood was collected from an indwelling cannula between 0 and 570 min. The mean incremental rise in plasma glucose after breakfast (δ peak/90 min) was 2.6 ± 0.5 (mean ±SEM mmol l−1 (pirenzepine) vs 4.5 ± 0.8 (placebo)), p < 0.05. Following exercise the fall in plasma glucose (δ gluc90–240 min) was 6.4 ± 1.9 (pirenzepine) vs 2.0 ± 1.3 (placebo), p < 0.005. The exercise‐related peak rise in GH was 12.6 ± 3.3 (pirenzepine) vs 28.5 ± 6.0 mU l−1 (placebo), p = 0.08. Excluding one outlying result there was an inverse correlation between the integrated exercise‐related increase in GH between 90 and 240 min and the fall in glucose over the corresponding time period (n = 11, r = −0.75, p = 0.008). In conclusion suppression of exercise‐related GH secretion by pirenzepine is associated with a subsequent lowering of plasma glucose levels. The smaller post‐prandial glucose rise pre‐exercise implies also a direct effect of pirenzepine on meal‐related glucose tolerance in Type 1 diabetes.
Randomized Trial Comparing Nicotinamide and Nicotinamide Plus Cyclosporin in Recent Onset Insulin‐dependent Diabetes (IMDIAB 1)
Authors: Pozzilli P. , Visalli N. , Boccuni M.L. , Baroni M.G. , Buzzetti R. , Fioriti E. , Signore A. , Cavallo M.G. , Andreani D. , Lucentini L. , Crinò A. , Cicconetti C.A. , Teodonio C. , Amoretti R. , Pisano L. , Pennafina M.G. , Santopadre G. , Marozzi G. , Multari G. , Campea L. , Suppa M.A. , De Mattia G.C. , Cassone‐Faldetta M. , Marietti G. , Perrone F. , Greco A.V. , Ghirlanda G. ,   The IMDIAB Study Group
Published: July 2009

A 1‐year open randomized controlled multicentre trial was carried out on 90 patients with recent onset (< 4 weeks) insulin‐dependent diabetes (IDDM) to compare the effect of nicotinamide (NCT) with the combination NCT and low dose cyclosporin (CyA) on clinical remission and optimization of metabolic control during the first year from diagnosis. Three groups of patients were randomly assigned to receive for 12 months either NCT 25 mg kg−1 day−1 (n = 30) or NCT 25 mg kg−1 day−1 + CyA 5 mg kg−1 day−1 (n = 30), the latter adjusted to maintain 12 whole blood trough levels of 83 nmol l−1; a third group of patients (n = 30) receiving insulin only acted as a control group for spontaneous remission and metabolic control. Clinical remission (i.e. suspension of insulin therapy with normal metabolic parameters for more than 2 weeks according to the International Diabetes Immunotherapy Group) was achieved at 3 months in 6/30 NCT treated patients and in 1/30 NCT + CyA treated patient (p = 0.05); no remission was observed in control patients. At 6 months the number of patients achieving remission in each group was 4/29, 3/27, and 1/29, respectively (p = NS). One year after diagnosis 4/27 NCT treated, 2/25 NCT+ CyA treated but 0/28 of the control patients were in remission (NCT vs control p = 0.05). Clinical remission lasted longer (7 ± 3 SD months) in NCT treated patients than in NCT+ CyA treated or control patients (p < 0.02). In patients who did not show clinical remission, there were no significant differences in the integrated measures of metabolic control (HbA1 and C peptide) between the two groups; however, NCT+ CyA treated patients only required significantly less insulin at 12 months compared to control patients (p < 0.02). Side‐effects were not observed in patients receiving NCT and were minimal in those treated with the combination of NCT+ CyA. We conclude that nicotinamide alone is a safe and effective adjunct to insulin in the early phase of IDDM to increase the rate of clinical remission and to improve integrated parameters of metabolic control.
Are Information Leaflets Given to Elderly People with Diabetes Easy to Read?
Authors: Petterson T. , Dornan T.L. , Albert T. , Lee P.
Published: July 2009

This study examined 15 different leaflets routinely given to elderly patients in the diabetes unit of a teaching hospital. It used (1) a Fog Index to give a rough guide of readability, and(2) examined the size and style of print. Results were compared with those of information leaflets taken from the hospitals' acute elderly care unit, rehabilitation unit, physiotherapy department, day hospital and outpatients department. Seven out of a total 70 leaflets (10%) were as hard to read as the British Medical Journal. None of these came from the diabetes unit, which may be because the diabetes leaflets were prepared by educators with considerable experience in communicating with patients. However, the authors' awareness of the need to use simple language was greater than their awareness of the need to use legible type. Eleven of the 15 leaflets from the diabetes unit (73%) failed to meet guidelines suggested by the Royal National Institute for the Blind, a rate which differed little from the overall rate (77%). These findings suggest that those resopnsible for producing patient information should be more aware of the principles of effective written communication.
Co‐ordination of Diabetes Care in the Primary and the Secondary Health Care System in Denmark
Authors: Olivarius N. de F. , Lauritzen T. , Beck‐Nielsen H. , Fog J. , Mogensen C.E. ,   Working Party, appointed by the Danish National Board of Health
Published: July 2009

In Denmark the co‐operation between the primary and secondary health care system is organized through referrals. Recommendations for improving interaction between the diabetes team (diabetologists, diabetes nurses, dietitians, chiropodists etc.) at the diabetes clinic, and general practice have been prepared by a working party for the Danish National Board of Health. General recommendations: (a) Appointment of a liaison committee in each county consisting of general practitioners (GPs), diabetologists, administrators, etc. (b) Employment of a GP at the diabetes clinic to take care of improving communication, teaching, research, quality assessment, etc. (c) Referral of all newly diagnosed patients with Type 1 diabetes and younger or complicated patients with Type 2 diabetes to the diabetes clinic. More far‐reaching forms of co‐operation to be discussed in the liaison committees include: (a) Based upon his own knowledge of where to look for help to solve a specific health problem, the diabetic patient may on his own initiative consult either the diabetes clinic or general practice. (b) Provision of access to consult the diabetes nurse/dietitian at the diabetes clinic for instruction without a formal referral. (c) Patients treated solely in general practice and thus unknown to the diabetes clinic may be referred or reported systematically to the diabetes clinic.
Infections and Diabetes: Mechanisms and Prospects for Prevention
Authors: Pozzilli P. , Leslie R.D.G.
Published: July 2009

Infections remain a serious hazard for the diabetic patient. Good metabolic control is a major factor in limiting the development and spread of infections and, most importantly, the development of diabetic complications which predispose to infections. In some patients recurrent infections can pose a problem, particularly if there is evidence of secondary immunodeficiency. In these patients adjuvant therapies, including Biological Response Modifiers (BRMS) should be considered. Several factors could predispose diabetic patients to infections. These factors include: genetic susceptibility to infection; altered cellular and humoral immune defence mechanisms; local factors including poor blood supply and nerve damage, and alterations in metabolism associated with diabetes. In the context of a diabetic patient all or some of these factors may operate. The purpose of this review is to assess the relative contribution of these potential mechanisms in leading to infection in patients with diabetes.
Apolipoprotein D Gene Polymorphism: A New Genetic Marker for Type 2 Diabetic Subjects in Nauru and South India
Authors: Baker W.A. , Hitman G.A. , Hawrami K. , McCarthy M.I. , Riikonen A. , Tuomilehto‐Wolf E. , Nissinen A. , Tuomilehto J. , Mohan V. , Viswanathan M. , Snehalatha C. , Ramachandran A. , Dowse G.K. , Zimmet P. , Serjeantsona S.W.
Published: July 2009

Type 2 diabetes is characterized by abnormalities in both glucose and lipoprotein metabolism and genes involved in lipid metabolism are legitimate candidates for involvement in Type 2 diabetes. We have previously reported an association in Nauruans between a Taq 1 polymorphism of the apolipoprotein D gene (apo D) and Type 2 diabetes. In this study these findings were investigated further in the Nauruan population as well as two other ethnic groups. In South Indian subjects, there was a significant difference in genotype distribution of apo D genotypes between diabetic subjects (n = 110) and controls (n = 88; p = 0.004) which was similar to that previously found in the Nauruan subjects. No such association was seen in elderly Finnish subjects (diabetic n = 69; impaired glucose tolerance n = 26 and normal glucose tolerance n = 31). Linkage between the apo D polymorphism and diabetes in 12 Nauruan families was only excluded under a highly penetrant dominant model and was unlikely under other single gene models. Since the β cell glucose transporter gene (Glut 2) is found in a similar chromosomal location to apo D, South Indian subjects (diabetic n = 95 and controls n = 56) were typed at this locus. No association between diabetes and the Glut 2 Taq I polymorphism was found in the South Indian subjects. Furthermore, there was no evidence of linkage disequilibrium between the apo D and Glut 2 genes. In conclusion, apo D might act as a modifying gene for Type 2 diabetes in some ethnic groups.
Mortality in Diabetic Subjects: An Eleven‐year Follow‐up of a Community‐based Population
Authors: Walters D.P. , Gatling W. , Houston A.C. , Mullee M.A. , Julious S.A. , Hill R.D.
Published: July 2009

In 1979, all the known diabetic subjects (849) were identified from a community (population 81851), of whom 717 (85%) were reviewed by a single observer. Using the NHS Central Register, follow‐up was completed for 98% of subjects. After 11 years, 306 (42.7%) diabetic subjects had died, of whom 65 were insulin treated and 241 were non‐insulin treated. Circulatory disease accounted for 168 (54.9%) deaths, of which 124 (73.8%) were due to ischaemic heart disease. The standardized mortality ratio (SMR) for all causes of death, based on data from England and Wales, was significantly raised for both insulin‐treated and non‐insulin‐treated patients (1.75, 95% CI 1.35 to 2.24 and 1.32, 95% CI 1.15 to 1.50, respectively). SMRs for all cause mortality were significantly greater for diabetic subjects in the 45–64 (SMR, 1.97, 95% CI 1.34 to 2.80), 65–74 (SMR 1.59, 95% CI 1.27 to 1.97 and 75 years and over (SMR, 1.26, 95% CI 1.08 to 1.45) age ranges. Using a proportional hazards model, after adjusting for age and gender, systolic blood pressure and vibration threshold were significant predictors of all cause mortality in insulin‐treated subjects. For non‐insulin‐treated subjects, blood glucose, systolic blood pressure, glycated haemoglobin, retinopathy, proteinuria, coronary artery disease, and stroke were significant baseline predictors of mortality. No association was found for serum cholesterol, body mass index, diastolic pressure or cigarette smoking in either treatment group.
Hospital Admissions and Social Deprivation of Patients with Diabetes Mellitus
Authors: Caddick S.L. , McKinnon M. , Payne N. , Ward T.J. , Thornton‐Jones H. , Kells J. , Ward J.D.
Published: July 2009

This study examined the relationship between hospital admissions for patients with diabetes mellitus and residence in an area of social deprivation. Admissions of patients with diabetes mellitus were identified during a 5‐year period between 1987 and 1992 using the district patient information service. All persons admitted were assigned to an electoral ward on the basis of their postcode. Age standardized admission rates were compared to the Townsend Deprivation Score for each electoral ward. A positive correlation was found between age standardized admission rate and Townsend Score (r = 0.76, p < 0.001). We believe this has significance for planning health care resources.
Variations in the Management of Diabetic Ketoacidosis in Children
Authors: Edge J.A. , Dunger D.B.
Published: July 2009

Cerebral oedema which develops during the treatment of diabetic ketoacidosis is an important cause of mortality and morbidity in children. We examined 25 management protocols from throughout the UK and related variations in fluid, bicarbonate, insulin, and potassium regimens to the incidence of cerebral oedema recalled in each centre. Treatment of shock ranged from 5 to 25 (median 20) ml kg‐1 plasma (5 recommended 0.9% saline only) over 10–60 min. Subsequent fluid regimens used 0.9% saline in 24 (0.45% saline in 1); 8 used 0.45% saline if hypernatraemia was present. The rehydration period ranged from 24 h (n = 20) to 48 h (n = 1) and was based on steady (n = 12) or irregular (n = 13) replacement. The quantity of potassium added to fluids was 20–80 (median 30) mmol I−1. Eight centres recalled having seen 1–5 (median 2) cases of cerebral oedema in the past 5 yr, 10 centres recalled none. Compared with the 10 centres without cerebral oedema, protocols from the 8 with cerebral oedema used more plasma to resuscitate (22 ± 3 (mean ± SD) vs 18 ± 4ml kg−1; p < 0.025), suggested larger maintenance fluid volumes for ages 6–9 yr (81 ± 2 vs 70 ± 11 ml kg−1 day−1; p < 0.005) and were more likely to change to 0.18% saline when blood glucose had fallen (8/8 vs 5/10) than 0.45% saline (0/8 vs. 5/10; p < 0.05).

Free water overload may contribute to cerebral oedema. These data strengthen the case for a nationally agreed protocol and a prospective study of the antecedents to the development of cerebral oedema.
Development of a Type 2 Diabetes Symptom Checklist: a Measure of Symptom Severity
Authors: Grootenhuis P.A. , Snoek F.J. , Heine R.J. , Bouter L.M.
Published: July 2009

The aim of the present study was to develop a Type 2 diabetes symptom checklist for use in clinical and epidemiological research, which can measure differences in symptom severity between patients and detect changes over time within patients. Face and content validity of items and dimension structure were based on literature and experiences of diabetologists. Two Likert scales were used to measure symptom frequency and perceived burden. Reliability, responsiveness and validity were studied in 185 Type 2 diabetic patients. Factor‐analysis confirmed the predesigned dimension structure with 34 items, distributed over 6 dimensions. The internal consistency with Cronbach α coefficients between 0.76 and 0.95 and test‐retest reliability with Pearson product‐moment correlation coefficients between 0.79 and 0.94 were satisfactory. The ability to detect change over time (responsiveness) was estimated in stable subjects, using sample size calculations. A minimal detectable mean change of 0.07‐0.58 points in total score on the 10‐point scale within a group of 100 subjects suggests an impressive responsiveness. Significant differences in symptom severity score were found between patients with different co‐morbidity status and treatment modes, indicating satisfactory construct validity of the dimension structure. The Type 2 Diabetes Symptom Checklist was found to be a useful diabetes‐specific symptom severity assessment method for clinical and epidemiological studies.
Increases in Serum Lipids During Pregnancy in Type 1 Diabetic Women with Nephropathy
Authors: Biesenbach G. , Janko O. , Stöger H. , Zazgornik J.
Published: July 2009

During pregnancy women with Type 1 diabetes do not differ from normal women with respect to pregnancy‐associated changes in serum lipid levels. However influence of diabetic nephropathy on lipoprotein metabolism in pregnancy has not been described previously. Changes in lipids were compared during and after pregnancy in 10 Type 1 diabetic women without macroproteinuria as well as in 5 diabetic women with macroproteinuria due to diabetic nephropathy. In the pregnant women with macroproteinuria, compared to the diabetic women without macroproteinuria, we observed both significantly higher total and percent increases in serum levels of total cholesterol (97% versus 48%) and of LDL‐cholesterol (137% versus 50%), which had risen progressively throughout gestation. The percent increases in serum triglycerides (115% versus 128%) were similar in both patient groups. Metabolic control was improved during pregnancy in both groups of women. Renal function remained normal throughout pregnancy in the diabetic women without nephropathy and worsened during pregnancy in the proteinuric women. The mean protein excretion showed a physiological rise from 0.107 ± 0.040 g 24 h−1 before pregnancy to 0.336 ± 0.234 g 24 h−1 in the third trimester in the non‐proteinuric women, and an increase from 2.2 ± 1.0 to 7.1 ± 1.7 g 24 h−1 during the same period in the women with macroproteinuria. Therefore, it is concluded that the greater increase in serum lipid levels during pregnancy in the women with pre‐existing diabetic nephropathy can mainly be explained by the concomitant increase in proteinuria associated with development of the nephrotic syndrome in these patients.
Lipid Composition of Platelets in Patients with Non‐insulin‐dependent Diabetes Mellitus: Studies Before and After Treatment of Diabetes
Authors: Tamasawa A. , Onuma T. , Tsutsui M. , Boku A. , Ochiai S. , Takebe K.
Published: July 2009

The study was designed to investigate whether impaired composition of platelet lipids in untreated diabetic patients improved after diabetic treatment. Fourteen untreated patients with non‐insulin‐dependent diabetes mellitus (NIDDM) and 15 healthy control subjects were studied. In the diabetic patients, the ratio of free cholesterol to phospholipid (FC/PL) in platelets of 0.33 ± 0.02 (mean ± SEM) at pre‐treatment, which was statistically (p < 0.05) higher than that of 0.26 ± 0.02 in control subjects, was significantly decreased to the value of 0.29 ± 0.02 (p < 0.01) after insulin therapy. Platelet FC level of 9.77 ± 0.77 μg 10−8 cells pre‐treatment was significantly (p < 0.01) reduced to the value of 7.72 ± 0.38 μg 10−8 cells post‐treatment. Platelet PL level showed no significant changes after the treatment. There was a significantly (p < 0.01) positive correlation between the decrease in FC/PL of platelets and that in haemoglobin A1c (HbA1c) after treatment for diabetes (rs = −0.729). These results indicate that the impaired lipid composition in platelets can be improved after an adequate glycaemic control in patients with NIDDM.
Latent Autoimmune Diabetes Mellitus in Adults (LADA): the Role of Antibodies to Glutamic Acid Decarboxylase in Diagnosis and Prediction of Insulin Dependency
Authors: Zimmet P. , Tuomi T. , Mackay I.R. , Rowley M.J. , Knowles W. , Cohen M. , Lang D.A.
Published: July 2009

Type 1 diabetes mellitus in adults may present in a manner similar to that of Type 2 diabetes but with a late development of insulin dependency. We studied 65 patients who presented with ‘adult‐onset’ diabetes after the age of 30 years. Of these patients, 19 required insulin therapy. The insulin‐treated patients were significantly younger, their onset of diabetes was at an earlier age, and their postprandial serum C‐peptide levels were lower than those of the non‐insulin‐treated group. Moreover, the insulin‐treated subjects had a higher mean concentration of antibodies to glutamic acid decarboxylase (GAD) (66.8 ± 10.2 units) than the patients who did not require insulin (9.9 ± 1.9 units) (p < 0.001) and their frequency of anti‐GAD positivity was 73.7% versus 4.3% (p < 0.001). Thus, among patients attending a diabetes clinic, the majority (73.7%) of subjects who presented with diabetes after 30 years of age and who subsequently required therapy with insulin, actually have the islet cell lesion of Type 1 diabetes which progresses at a slower tempo than in children. We conclude that testing for anti‐GAD in adult‐onset non‐obese diabetic patients should be a routine procedure in order to detect latent insulin‐dependency at the earliest possible stage, since this assay can assist in the correct classification of diabetes, and more appropriate therapy.
Localization of Fibril/Microfibril and Basement Membrane Collagens in Diabetic Glomerulosclerosis in Type 2 Diabetes
Authors: Makino H. , Shikata K. , Wieslander J. , Wada J. , Kashihara N. , Yoshioka K. , Ota Z.
Published: July 2009

Collagen is one of the major components of the extracellular matrices of the kidney. Basement membrane collagen, type IV collagen, is the major component in normal glomeruli. Fibril and interstitial collagen such as type III collagen, type V collagen, and type VI collagen are minor components of glomerular extracellular matrices and are localized mainly in the interstitium. Diabetic glomerulosclerosis is characterized by the expansion of the glomerular mesangial matrix as well as by thickening of the glomerular basement membrane. In order to clarify the roles of these various types of collagen in the development of diabetic glomerulosclerosis, immunohistochemical studies were perfomed in kidney specimens from patients with Type 2 diabetes. Early glomerulosclerosis is characterized by expansion of mesangial matrix with basement membrane collagen. However, in later stages glomerulosclerosis is characterized by an increase in the minor collagen components, such as type V and type VI collagen or collagens not normally present, such as type III collagen. Mesangial cells are known to synthesize all these types of collagen. In diabetes, phenotypic change in mesangial cells might produce excess amounts of fibril and interstitial collagen such as type III, type V, and type VI collagen, thus, leading to glomerulosclerosis.
High β‐Glucan Oat Bran and Oat Gum Reduce Postprandial Blood Glucose and Insulin in Subjects With and Without Type 2 Diabetes
Authors: Braaten J.T. , Scott F.W. , Wood P.J. , Riedel K.D. , Wolynetz M.S. , Brulé D. , Collins M.W.
Published: July 2009

The aim of the current study was to characterize the effects of isolated and native sources of β‐glucan, oat gum, and oat bran, respectively, when incorporated into a complete meal. Fasting control subjects and subjects with Type 2 diabetes were fed porridge meals containing either wheat farina, wheat farina plus oat gum or oat bran. Blood samples were collected for 3 h after the test meals and plasma glucose and insulin were measured. Oat bran and wheat farina plus oat gum meals reduced the postprandial plasma glucose excursions and insulin levels when compared with the control wheat farina meal in both control and Type 2 diabetic subjects. This study shows that both the native cell wall fibre of oat bran and isolated oat gum, when incorporated into a meal, act similarly by lowering postprandial plasma glucose and insulin levels. A diet rich in β‐glucan may therefore be of benefit in the regulation of postprandial plasma glucose levels in subjects with Type 2 diabetes.
A Novel Capillary Collection Method for Obtaining Current Glycosylated Haemoglobin Levels in Diabetic Children
Authors: Shah A.R. , Challener J. , Elsey T.S. , Maguire G.A. , Calvin J. , Rayman G.
Published: July 2009

A simple method for collecting capillary blood for measurement of glycosylated haemoglobin (HbA1c) was developed that allows samples to be obtained at home and then mailed to the laboratory 2 weeks before a hospital visit. A single drop of blood is collected into a 2 ml plastic tube and sent for HbA1c assay on the Diamat HPLC system which has inter‐and intra‐assay coefficients of variation < 2.6 and < 1.2%, respectively. Results of simultaneously obtained venous and capillary samples in 32 diabetic children agreed well with each other. A separate study of 25 patients was performed to determine whether transport conditions affected the samples. Posted samples were compared with venous samples; again the values were in good agreement. This method is now used routinely in the diabetic clinic. Its value was determined by questionnaire in 40 children with age range 4–17 years. No family experienced difficulty collecting samples and all samples received were suitable for analysis. Children preferred this method to blood collection in the clinic as they felt it was less traumatic and more convenient. Seventy‐nine percent of them understood its value in the long‐term control of diabetes. In 40.5% of visits changes to management were made at the clinic due to the availability of the results.
Circadian Blood Pressure Levels in Normotensive Normoalbuminuric Type 1 Diabetic Patients
Authors: Sivieri R. , Deandrea M. , Gai V. , Cavallo‐Perin P.
Published: July 2009

Increase in blood pressure and its circadian alterations in Type 1 diabetes are usually associated with diabetic nephropathy. To evaluate if diabetes itself could be responsible for the observed increase in blood pressure levels, we studied a group of 17 normotensive, normoalbuminuric Type 1 diabetic patients with a disease duration more than 15 years, with no clinical evidence of autonomic neuropathy or ischaemic heart disease, and without any known determinant of hypertension, and a control group of 17 normal subjects, normotensive, each matched for sex, age, BMI, albumin excretion rate, and clinical blood pressure to a diabetic subject. In both groups an ambulatory blood pressure monitoring was performed through an oscillometric recorder. The mean systolic and diastolic ambulatory blood pressure values were significantly higher in diabetic patients (p <0.001) in the 24‐h analysis and during waking and sleeping periods. The night/day ratio of systolic and diastolic blood pressure were not significantly different in patients and controls, as well as heart rate values and heart rate variability. We conclude that mechanism(s) inherent to the diabetic condition other than diabetic nephropathy or autonomic neuropathy could be responsible for blood pressure evaluation in normotensive Type 1 diabetes with normoalbuminuria.
Predictors of Glycaemic Control in Type 1 Diabetic Patients after Participation in an Intensified Treatment and Teaching Programme
Authors: Bott U. , Jörgens V. , Grüsser M. , Bender R. , Mühlhauser I. , Berger M.
Published: July 2009

The aim of the study was to identify predictors of long‐term glycaemic control in Type 1 diabetic patients after participation in an intensified insulin treatment and teaching programme. The study population consisted of 697 Type 1 diabetic patients (mean age 26 ± 7 (SD) years, duration of diabetes 8 ± 7 years) who participated in the same structured intensified insulin treatment and teaching programme in 10 hospitals and who were re‐examined after 1, 2, and 3 years. Multiple and logistic regression analyses were performed including a set of demographic, disease‐related, social, and psychosocial variables as potential predictors. As dependent variables the average HbA1 values during the 3‐year follow‐up period and a composite variable (average HbA1 values/frequency of severe hypoglycaemia)—dividing patients into three groups with good, moderate or poor metabolic control—were considered. Regression analysis of average HbA1 values revealed significance (p <0.05) for seven independent predictors in descending order: smoking, age at onset of diabetes, frequency of home blood glucose monitoring, socioeconomic status, diabetes‐related knowledge, perceived coping abilities, and sex (R2 (percentage of variation explained by the model) = 17%). In a second regression model, HbA1 values before the intervention programme were added to the model and achieved the highest standardized regression coefficient (0.38), increasing R2 to 29%. In the logistic regression models considering both HbA1 and severe hypoglycaemia as a composite dependent variable, diabetes‐related knowledge, HbA1 values before the intervention, smoking, perceived coping abilities, age at onset of diabetes, and C‐peptide levels were the strongest predictors of glycaemic control. In conclusion, the relationship between demographic, disease‐related, psychosocial, and social variables and metabolic control is complex. Therefore, simplistic concepts of linear causality should be abandoned. In addition to HbA1 values before the intervention, smoking, diabetes‐related knowledge, home blood glucose monitoring, age at onset of diabetes, perceived coping abilities and C‐peptide levels were the most significant and consistent predictors of glycaemic control.
Biomedical and Psychosocial Predictors of Early Rehospitalization Among Children With Insulin‐dependent Diabetes Mellitus: A Longitudinal Study
Authors: Charron‐Prochownik D. , Kovacs M. , Obrosky D.S. , Stiffler L.
Published: July 2009

The purpose of the present study was to determine the cumulative probability of the first diabetes‐related rehospitalization within the initial 2.5 years after the onset of insulin‐dependent diabetes mellitus (IDDM) among newly diagnosed children, and to identify risk factors that can be determined shortly after IDDM‐onset. The sample consisted of 88 children, 8 to 13 years old at the onset of IDDM, who had been participating in a longitudinal study. In this sample, there was a 0.25 cumulative probability of an early readmission. Poor control was the most frequent reason for readmissions. Four variables significantly increased the risk of early rehospitalization: severity of child's externalizing symptoms at IDDM‐onset, lower socio‐economic status, younger age at onset of IDDM, and higher levels of glycosylated haemoglobin, reflecting poorer metabolic control. Because externalizing symptoms and poor control are amenable to change, some early rehospitalizations can potentially be prevented. Furthermore, information about the risk of early rehospitalization should be part of initial diabetes education in order to better prepare families for the possibility of such an event.