bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of troglitazone administration to obese hyperglycaemic patients with near‐normoglycaemia
Authors: Sekino N. , Kashiwabara A. , Inoue T. , Kawasaki T. , Ogata N. , Sawashige K. , Yamanouchi T.
Published: December 2004

Aims:  We assessed the effectiveness of 400 mg/day of troglitazone administered to hyperglycaemic patients with near‐normoglycaemia who were obese and who had hyperinsulinaemia.

Results:  The area under the plasma glucose curve in oral glucose tolerance tests (OGTT) significantly decreased from 39.8 ± 19.4–20.5 ± 10.2 mg/dL · h and the area under the insulin‐response curve from 31.8 ± 22.5–12.2 ± 5.7 μU/ml · h 4 months after the start of treatment. The level of HbA1c significantly improved from 6.6 ± 0.2 to 6.3 ± 0.2% (p < 0.05) by 1 month after administration, and that of serum 1,5‐anhydroglucitol (1,5‐AG) from 12.6 ± 1.1–18.3 ± 2.5 μ/ml (p < 0.05). In some cases, recovery of the first‐phase insulin secretion was observed.

Conclusions:  These findings suggest that the administration of this insulin sensitizer is useful in the treatment of obese Japanese subjects with borderline or mild diabetics accompanied by hyperinsulinaemia.
Latin‐American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients
Authors: Halpern A. , Mancini M. C. , Suplicy H. , Zanella M. T. , Repetto G. , Gross J. , Jadzinsky M. , Barranco J. , Aschner P. , Ramirez L. , Matos A. G.
Published: December 2004

Aim:  To determine if obese non‐insulin‐dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat.

Design:  Double‐blind, parallel, randomized, placebo‐controlled, multicentre study.

Subjects:  Obese, non‐insulin‐dependent diabetic patients, aged 18–70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin‐American centres, in five countries.

Efficacy and Tolerability Measurements:  After screened, eligible patients passed by a 2‐week placebo run‐in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL‐cholesterol, LDL‐cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline.

Results:  After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 ± 0.23 vs. 2.58 ± 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost ≥ 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat‐treated patients had a mean decrease in glucose levels of 1.00 ± 0.34 mmol/l [3.7%] vs. 0.01 ± 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 ± 0.15 vs. a decrease of 0.22 ± 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL‐cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low.

Conclusion:  Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.
Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus
Authors: Ambrosch A. , Dierkes J. , Lobmann R. , Kühne W. , König W. , Luley C. , Lehnert H.
Published: December 2004

Aims  Limited data are available on determinants of diabetic neuropathy as its pathogenesis is multifactorial. Since homocysteine exhibits toxic effects on vascular endothelial cells, the association between homocysteine and the prevalence of neuropathy in Type 2 diabetes mellitus was investigated.

Methods  A total of 65 Type 2 diabetic patients were consecutively enrolled into the study. Neuropathy was diagnosed according to clinical symptoms, clinical examination, electrophysiological sensory testing and autonomic function testing. With regard to homocysteine‐related parameters, plasma homocysteine, folate, vitamin B12, vitamin B6 and renal function (creatinine, ceratinine clearance, cystatin C) were measured, and the C677T polymorphism of the methylenetetrahydrofolate reductase gene was determined.

Results  Forty‐three of the Type 2 diabetic patients were classified as suffering from neuropathy. Both patient groups were comparable with regard to demographic data, blood pressure, glucose metabolism, renal function and homocysteine‐related vitamins. In contrast, homocysteine levels (P = 0.04) and the frequency of hyperhomocysteinemia (≥ 15 μmol/l) (P = 0.01) were significantly increased in neuropathic patients. In a logistic regression model with neuropathy as dependent variable, homocysteine (adjusted for creatinine, homocysteine‐related vitamins, HbA1c and duration of diabetes) was the only significant variable associated with the prevalence of neuropathy (odds ratio for homocysteine per 5 μmol/l increase: 2.60 (95% confidence interval 1.07–6.33)).

Conclusion  The data indicate that homocysteine is independently associated with the prevalence of diabetic neuropathy in a collective of Type 2 diabetic patients. A larger, prospective study would be desirable to clarify the role of homocysteine in the pathogenesis of diabetic neuropathy.
Screening for Type 2 diabetes—should it be now?
Authors: Borch‐Johnsen K. , Lauritzen T. , Glümer C. , Sandbæk A.
Published: December 2004

Aims Screening for Type 2 diabetes has been recommended in several countries due to the increasing prevalence of diabetes. This review evaluates whether Type 2 diabetes is a disease that fulfils the criteria for screening set by the World Health Organization.

Methods Literature search was performed on the literature bases MedLine, Pub Medical, NIDDK, Cochrane Library and CINAHL using the MeSH terms ‘non‐insulin‐dependent‐diabetes‐mellitus’ and mass screening. Using this strategy we identified studies specifically evaluating screening strategies and diagnostic tests for Type 2 diabetes. The evaluation of psychosocial consequences included studies related to other chronic diseases. This literature was used to evaluate whether the WHO criteria for screening were fulfilled.

Results The papers were reviewed but a meta‐analysis was not possible, as no randomized controlled clinical trials were performed in the area of screening.

Conclusion Type 2 diabetes does not fulfil the criteria for population‐based mass screening. No screening and intervention studies have been performed, systematically evaluating the positive and negative effects of screening. Furthermore, intervention studies up until now have been restricted to clinically diagnosed patients with diabetes, and most of these have recruited patients with long diabetes duration and early complications. These groups will have a worse prognosis and thus probably show greater benefits of such intervention. Finally, the psychosocial and health economic consequences of screening and intervention for Type 2 diabetes are largely unknown. Thus, systematic screening and intervention trials should be encouraged, and meanwhile intensified case finding and opportunistic screening in high‐risk groups should be performed.

Diabet. Med 20, 175–181 (2003)
An unusual cause of diabetic ketoacidosis and fulminant septicaemia
Authors: Hassanein M. M. , Croall J. , Ewins D. L. , Worth R. C.
Published: December 2004

Background Diabetic ketoacidosis (DKA) is a common medical emergency. Resistant and recurrent DKA can be due to underlying infection, and a detailed travel history may be important in determining the cause in such cases. We report here a case of unusual DKA and fulminant septicaemia in a Caucasian male with Type 1 diabetes 2 years after returning from living in Thailand.

Case report A 39‐year‐old Caucasian male was diagnosed with Type 1 diabetes whilst working in Thailand where he also subsequently developed a cavitating lung lesion diagnosed locally as pulmonary tuberculosis. Two years after returning to the UK he was admitted with DKA and septicaemia. Despite correction of his DKA his condition deteriorated and he developed a fluid collection anterior to the left hip on computed tomography scanning. Blood and fluid aspirate cultures confirmed a diagnosis of melioidosis, a rare fulminant septicaemia in the UK, but endemic in South‐east Asia and tropical Australia. Full recovery followed changing antibiotics to intravenous ceftazidime with no relapse 3 years after acute episode.

Conclusions Physicians as well as microbiologists should consider melioidosis in anyone presenting with septicaemia and/or resistant DKA, especially if the history includes travel to endemic areas or if the cultures suggest Pseudomonas‐like organism. With increasing international travel, it is crucial to remember that good travel history could be life‐saving in some cases of septicaemia.

Diabet. Med. 20, 242–244 (2003)
Is birth weight related to later glucose and insulin metabolism?—a systematic review
Authors: Newsome C. A. , Shiell A. W. , Fall C. H. D. , Phillips D. I. W. , Shier R. , Law C. M.
Published: December 2004

Aim To determine the relationship of birth weight to later glucose and insulin metabolism.

Methods Systematic review of the published literature. Data sources were Medline and Embase. Included studies were papers reporting the relationship of birth weight with a measure of glucose or insulin metabolism after 1 year of age, including the prevalence of Type 2 diabetes mellitus (DM). Three reviewers abstracted information from each paper according to specified criteria.

Results Forty‐eight papers fulfilled the criteria for inclusion, mostly of adults in developed countries. Most studies reported an inverse relationship between birth weight and fasting plasma glucose concentrations (15 of 25 papers), fasting plasma insulin concentrations (20 of 26), plasma glucose concentrations 2 h after a glucose load (20 of 25), the prevalence of Type 2 DM (13 of 16), measures of insulin resistance (17 of 22), and measures of insulin secretion (16 of 24). The predominance of these inverse relationships and the demonstration in a minority of studies of other directions of the relationships could not generally be explained by differences between studies in the sex, age, or current size of the subjects. However, the relationship of birth weight with insulin secretion was inconsistent in studies of adults.

Conclusions The published literature shows that, generally, people who were light at birth have an adverse profile of later glucose and insulin metabolism. This is related to higher insulin resistance, but the relationship to insulin secretion in adults is less clear.

Diabet. Med. 20, 339–348 (2003)
Cause‐specific and total mortality in the Canterbury (New Zealand) insulin‐treated Diabetic Registry population: a 15‐year follow‐up study
Authors: Florkowski C. M. , Scott R. S. , Graham P. J. , Han D. Y. , Moir C. L.
Published: December 2004

Aims To establish all‐cause and cause‐specific death rates, and risk factors for mortality in insulin‐treated diabetic individuals living in the province of Canterbury, New Zealand.

Methods Insulin‐treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time.

Results There were 419 deaths in 11 226.3 person‐years of follow‐up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8–2.2). Relative mortality was greatest for the group aged 0–29 years (SMR 3.0 (95% CI 2.4–3.7)). After controlling for diabetes duration and gender, a 10‐year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29–36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10‐year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24–29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis.

Conclusions Mortality rates are high for insulin‐treated diabetic individuals relative to the general population.

Diabet. Med. 20, 191–197 (2003)
The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study
Authors: Bingham E. , Hopkins D. , Pernet A. , Reid H. , Macdonald I. A. , Amiel S. A.
Published: December 2004

Aims To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in β‐cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic β‐cell and the hypothalamic glucose‐sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain.

Methods Ten healthy males were studied on four occasions and in random order underwent three stepped hypoglycaemic (plasma glucose aims: 3.4, 2.8, 2.4 mmol/l) and one euglycaemic (plasma glucose aim: 5 mmol/l) insulin clamps. Prior to each hypoglycaemic study, volunteers received either 10 mg glibenclamide, or 5 mg/kg diazoxide or placebo orally. Cognitive function, symptom scores and counterregulatory hormone responses were measured at each glycaemic level.

Results There was no statistically significant effect of either drug on the symptoms generated or the counterregulatory hormonal response during hypoglycaemia. However, cognitive function was better preserved during hypoglycaemia in the glibenclamide‐treated arm, particularly four‐choice reaction time which deteriorated at a plasma glucose 2.5 mmol/l compared with 3.0 mmol/l with diazoxide (P = 0.015) and 2.9 mmol/l with placebo (P = 0.114).

Conclusions Single doses of pharmacological agents which alter membrane KATP channel activity do not affect the counterregulatory response to hypoglycaemia but may modify cognitive function during cerebral glucopenia. The unexpected effects of glibenclamide on cortical function suggest a novel action of sulphonylureas that warrants further investigation.

Diabet. Med. 20, 231–237 (2003)
Decreased red blood cell aggregation subsequent to improved glycaemic control in Type 2 diabetes mellitus
Authors: Chong‐Martinez B. , Buchanan T. A. , Wenby R. B. , Meiselman H. J.
Published: December 2004

Aims Reports of rheological changes following intensification of metabolic control are limited and not concordant. The present study was designed to test the hypothesis that intensification of management of Type 2 diabetes (T2DM) with diet, exercise and insulin improves haemorheological behaviour by reducing red blood cell (RBC) aggregation.

Methods Blood was sampled from 55 subjects before and following 14 ± 3 weeks of intensified management. RBC aggregation was measured in vitro for cells in plasma or in an aggregating 70 kD dextran solution. Plasma viscosity and whole blood viscosity were also measured.

Results During treatment, fasting glucose fell 27%, HbA1c fell 21%, and serum triglycerides and total cholesterol fell 28% and 12%, respectively (P < 0.0001 for each). The extent and strength of RBC aggregation in plasma fell by 10–13% (P < 0.002). Similar decreases of RBC aggregation were seen for cells suspended in dextran (P < 0.002). Plasma viscosity decreased by 3% (P < 0.02) and high shear blood viscosity by 6–7% (P < 0.0001). Changes of RBC aggregation in plasma and in dextran were significantly correlated, supporting a cellular rather than a plasmatic origin for these changes. However, there were no significant correlations between RBC aggregation changes and changes of fasting glucose, HbA1c, serum triglycerides, serum cholesterol, or plasma fibrinogen.

Conclusions Intensified metabolic control results in a reduction of RBC aggregation that appears to be intrinsic to RBC. Since increased RBC aggregation can impair microcirculatory flow, it is possible that haemorheological factors may contribute to the reduction of microvascular complications resulting from improved metabolic control in T2DM.
How should peripheral neuropathy be assessed in people with diabetes in primary care? A population‐based comparison of four measures
Authors: Rahman M. , Griffin S. J. , Rathmann W. , Wareham N. J.
Published: December 2004

Aims To test the accuracy of four measures of peripheral diabetic neuropathy in a primary care population.

Methods Type 2 diabetic (n = 544) and 544 non‐diabetic participants aged 45–76 years were randomly selected from general practice registers. Neuropathy was assessed using vibration threshold (VT) and scores for light touch, thermal sense and modified Michigan Neuropathy Screening Instrument questionnaire. These measures were assessed for variation with diabetes status, age, diabetes duration, HbA1c, and presence of retinopathy and nephropathy. Light touch, thermal sense and questionnaire scores were assessed against VT using ROC curve analysis.

Results Only VT and light touch were different between diabetic and non‐diabetic groups (P = 0.02 and < 0.0001, respectively). All measures were significantly associated with diabetes duration and retinopathy, and all except questionnaire score (P = 0.14) with age. None was associated with nephropathy and only questionnaire score was associated with HbA1c (P = 0.033). VT varied as expected across scores of light touch (χ2 = 41.65, P = 0.0001), thermal sense (χ2 = 15.86, P = 0.015) and questionnaire (χ2 = 21.22, P = 0.047). Area under the curve values for light touch, thermal and questionnaire scores were 0.72 (95% confidence interval (CI) 0.63, 0.82), 0.63 (95% CI 0.52, 0.73) and 0.64 (95% CI 0.53, 0.74), respectively.

Conclusions All measures had associations with risk factors for neuropathy, but light touch score (monofilament) had the strongest association with vibration threshold (the chosen gold standard) and thus appeared the most appropriate tool for use in primary care, because of its validity and simplicity of use.

Diabet. Med. 20, 368–374 (2003)
Metabolic and cardiovascular effects of very‐low‐calorie diet therapy in obese patients with Type 2 diabetes in secondary failure: outcomes after 1 year
Authors: Dhindsa P. , Scott A. R. , Donnelly R.
Published: December 2004

Aims To evaluate the short‐term and 1‐year outcomes of an intensive very‐low‐calorie diet (VLCD) on metabolic and cardiovascular variables in obese patients with Type 2 diabetes (T2DM) and symptomatic hyperglycaemia despite combination oral anti‐diabetic therapy ± insulin, and to assess patient acceptability and the feasibility of administering VLCD treatment to this subgroup of patients in a routine practice setting.

Methods Forty obese patients with T2DM (22 M, mean age 52 years, body mass index (BMI) 40 kg/m2, duration of T2DM 6.1 years) and symptomatic hyperglycaemia despite combination oral therapy (n = 26) or insulin + metformin (n = 14) received 8 weeks of VLCD therapy (750 kcal/day) followed by standard diet and exercise advice at 2–3‐month intervals up to 1 year. Insulin was discontinued at the start of the VLCD, and anti‐diabetic therapy was adjusted individually throughout the study, including (re)commencement of insulin as required.

Results Immediate improvements in symptoms and early weight loss reinforced good compliance and patient satisfaction. After 8 weeks of VLCD, body weight and BMI had fallen significantly: 119 ± 19–107 ± 18 kg and 40.6–36.6 kg/m2, respectively, with favourable reductions in serum total cholesterol (5.9–4.9 mm), blood pressure (10/6 mmHg) and fructosamine (386 ± 73–346 ± 49 µm) (equates to an HbA1c reduction of approximately 1%). Sustained improvements were evident after 1 year, with minimal weight regain, e.g. mean body weight 109 ± 18 kg and BMI 37 ± 4 kg/m2. Glycaemic control tended to deteriorate after 1 year.

Conclusions The absence of a control group is a major limitation, but the results indicate that 8 weeks of VLCD treatment may be effective and well tolerated in symptomatic obese patients with T2DM in secondary failure, producing sustained cardiovascular and metabolic improvements after 1 year. VLCD therapy is a treatment option that deserves greater consideration in this difficult‐to‐treat patient population.
An assessment of care of paediatric and adolescent patients with diabetes in a large district general hospital
Authors: Barton D. M. , Baskar V. , Kamalakannan D. , Buch H. N. , Gone K. , Wilson E. , Anderson J. , Abdu T. A. M.
Published: December 2004

Aims To assess the process of clinical care and outcomes of young patients with diabetes attending clinics at a large district general hospital.

Methods Retrospective analysis of data obtained from 106 case notes of patients aged 12–22 years attending the paediatric, combined adolescent or adult diabetes clinics between 1998 and 2000. The frequency of follow‐up, rate of admission, glycaemic control, systolic blood pressure, weight change and screening for complications were assessed.

Results The mean attendance rate was 78%. The admission rate was 91 admissions per 1000 patient years. Overall, the mean HbA1c was 9.1% with only 15% of paediatric and adolescent patients having mean HbA1c≤ 8.0%. Mean systolic blood pressure was 124 mmHg. There was a significant increase in obesity with mean weight for height at diagnosis increasing from 89% to 111% after 7 years of diabetes. Mean daily insulin dose was 1.51 U per kg body weight and decreased with increasing age. Screening for complications and associated conditions was variable: 91% for retinopathy, 86% for foot problems, 64% for thyroid dysfunction, 22% for coeliac disease and 10% for microalbuminuria. The overall rate of retinopathy was low at 4% of those screened.

Conclusions Providing satisfactory care for young people with diabetes remains a difficult challenge. Although the complication rate observed was low in this group, the most important issues are the need for improvement in glycaemic control, weight gain and high drop‐out rate.

Diabet. Med. 20, 394–398 (2003)
The cost‐effectiveness of continuous subcutaneous insulin infusion compared with multiple daily injections for the management of diabetes
Authors: Scuffham P. , Carr L.
Published: December 2004

AimsTo estimate the cost effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) for patients using insulin pumps.

MethodsWe constructed a Markov model to estimate the costs and outcomes for patients with insulin‐dependent diabetes (IDDM) treated with CSII using an insulin pump compared with MDI. Key parameters were obtained from the published scientific literature. The primary outcome was quality‐adjusted life years (QALYs). Monte Carlo simulations were undertaken for 10 000 hypothetical patients over 8 years of monthly cycles (the expected life of a pump).

ResultsOver an 8‐year period an average patient could expect to gain 0.48 [standard deviation (sd) 0.20] QALYs using CSII compared with MDI. The additional cost over 8 years for this gain was £5462 (sd£897). The incremental cost per QALY was £11 461 (sd£3656). CSII was most cost‐effective in patients who had more than two severe hypoglycaemic events per year and who required admission to hospital at least once every year. Cases where CSII might be not economically viable are cases where diabetes is well controlled with few severe hypoglycaemic events. Results were most sensitive to the number of hypoglycaemic events per patient and the utility weights used to estimate QALYs.

ConclusionCSII is a worthwhile investment when targeted to those who might benefit most.

Diabet. Med. 20, 586–593 (2003)
Safety and efficacy of insulin glargine (HOE 901) versus NPH insulin in combination with oral treatment in Type 2 diabetic patients
Authors:   HOE 901/2004 Study Investigators Group
Published: December 2004

Aims A European, randomized, 29‐centre, open‐label study compared the safety and efficacy of two formulations of insulin glargine and neutral protamine Hagedorn (NPH) human insulin, in combination with oral agents, in patients with Type 2 diabetes mellitus (DM).

Methods Two‐hundred‐and‐four patients with Type 2 DM, in whom oral treatment alone was inadequate, were randomized to insulin glargine with 30 µg/ml zinc [insulin glargine (30)], or insulin glargine with 80 µg/ml zinc [insulin glargine (80)] or NPH insulin subcutaneously once daily. Insulin was titrated to aim for fasting blood glucose (FBG) values between 4 and 7 mmol/l. All participants received oral therapy during the 3‐week titration phase and 1‐week maintenance phase of the trial.

Results No differences between treatment groups were observed in adjusted mean fasting plasma glucose; significant decreases of 3.4 mmol/l, 3.5 mmol/l and 3.1 mmol/l were observed within the insulin glargine (30), insulin glargine (80) and NPH insulin groups, respectively (P < 0.0001 in each case). No differences between groups, but significant changes within groups, were observed in self‐monitored FBG, mean FBG, blood glucose profile, stability of FBG, nocturnal blood glucose, fasting serum C‐peptide, non‐esterified fatty acids, haemoglobin A1c, fructosamine and fasting serum insulin. A significantly greater proportion of NPH insulin patients experienced symptomatic nocturnal hypoglycaemia (19.1 NPH group vs. 7.3% glargine groups; P = 0.0123). Both insulins were well tolerated; one patient in each group experienced an injection site reaction.

Conclusions Insulin glargine is as safe and effective as NPH insulin given once daily and in this study caused fewer episodes of nocturnal hypoglycaemia.

Diabet. Med. 20, 545–551 (2003)
Hypertension in people with Type 2 diabetes: knowledge‐based diabetes‐specific guidelines
Authors:   Working Party of the International Diabetes Federation (European Region)
Published: December 2004

The International Diabetes Federation (Europe) has updated these guidelines on hypertension management specifically in Type 2 diabetes in the light of recent results of the first prospective, randomized controlled studies to investigate clinical outcomes in people with diabetes and hypertension. The guidelines are knowledge based, i.e. based not only on evidence originating from clinical trials, but also from epidemiological and pathophysiological studies. A successful management strategy requires the following components:

Regular surveillance to detect developing hypertension and other cardiovascular (CV) risk factors.

Considering more frequent monitoring and review of CV risk factors if any single blood pressure (BP) measurement > 140/85 mmHg (or 130/75 if microalbuminuria); when appropriate, using ambulatory or home monitoring to establish the baseline BP.

Considering other CV risk factors, such as a raised albumin excretion rate, in setting the intervention threshold.

Individualizing the target BP in accordance with other CV risk factors.

Agreeing lifestyle and therapeutic interventions with the patient, with education and empowerment as required.

Implementing lifestyle modifications, including controlling calorie, salt and alcohol intake, increased physical activity, weight control and smoking cessation.

Therapeutic strategy: the primary goal of therapy is to reduce BP markedly. Combination therapy is often necessary, e.g. an angiotensin converting enzyme (ACE) inhibitor and a diuretic. Some classes are particularly useful for certain patients, notably longer‐acting ACE inhibitors, angiotensin 2 receptor antagonists (A2RAs) and calcium antagonists in those at risk of diabetic nephropathy, loop diuretics and thiazides in those at risk of hyperkalaemia, β‐blockers and calcium antagonists (except short‐acting dihydropyridines) in patients with angina, β‐blockers and ACE inhibitors after a myocardial infarction or in those with left ventricular dysfunction, and thiazide diuretics and long‐acting dihydropyridine calcium antagonists for isolated systolic hypertension. A2RAs should be particularly considered when ACE inhibitors are not tolerated. α1‐Blockers should not be considered first line in the absence of outcome data. Cost of drugs will modify these strategies in developing countries.

Monitoring response to therapies and, if target levels are not achieved, either intensifying drug therapy if the CV risk justifies it, or reassessing the target.

Maintaining a quality assurance strategy.

This strategy is summarized in a simple, practical management algorithm.
The impact of screening for Type 2 diabetes in siblings of patients with established diabetes
Authors: Farmer A. J. , Doll H. , Levy J. C. , Salkovskis P. M.
Published: December 2004

Background  Targeted screening for Type 2 diabetes has been proposed as a method of identifying people with, or at risk of, the disease in order to implement preventive care.

Aim  To assess the changes in anxiety, well‐being, and cognitions associated with screening for Type 2 diabetes in people at increased risk of diabetes after 1 year; and to identify potential predictors of increased anxiety and lower well being over this period.

Design and setting  One‐year follow up of a cohort of non‐diabetic siblings of those with Type 2 diabetes registered with general practitioners in Oxfordshire and Northamptonshire who were identified for participation in a programme to undertake sib‐pair genetic analysis.

Methods  Potential families were selected through identification of people with Type 2 diabetes. Family members aged 35–74 years, who did not have diabetes and who were willing to participate in the study, completed measures before receiving the results of a fasting plasma glucose test, and 1 year later. Measures included the Spielberger State Anxiety Scale‐short form (SSAI‐SF), the Well‐Being Questionnaire 12 item scale (WBQ‐12), and measures of cognitions about developing diabetes. The Health Anxiety Inventory (HAI) was completed before receiving the results of the tests to assess its relationship with anxiety at 1 year.

Results  A cohort of 431 individuals was identified, of whom 328 (76%) returned fully completed WBQ scales both initially and at 1 year. State anxiety measured with the SSAI‐SF fell from 34.5 (95% CI 33.4–35.6) to 32.3 (31.2–33.4) at 1 year (P < 0.0001). Mean WBQ‐12 scores rose (i.e. improved) from 26.8 (26.0–27.4) to 27.4 (26.7–28.1) (P = 0.008). SSAI‐SF and WBQ‐12 mean scores over 1 year did not differ between participants receiving a normal or an at‐risk test result. However, those receiving an at‐risk test result were more likely, at 1 year, to consider themselves at increased likelihood of developing diabetes (P < 0.001) and to report thinking about what it would be like to develop diabetes (P = 0.006). A score in the upper tertile of the initial HAI was associated with an increased level of anxiety at 1 year (adjusted odds ratio 2.0, 95% CI 1.2–3.4, P = 0.006).

Conclusions  There is no evidence that an ‘at‐risk’ test result leads to sustained anxiety or reduced well being at 1 year compared with those receiving a normal test result. However, further studies are required to clarify levels of anxiety prior to screening to assess the overall impact of the process.

Diabet. Med. **, ***–*** (2003)
Insulin sensitivity in physically fit and unfit children of parents with Type 2 diabetes
Authors: Ahn C. W. , Song Y. D. , Nam J. H. , Kim D. M. , Woo S. O. , Park S. W. , Cha B. S. , Lim S. K. , Kim K. R. , Lee J. H. , Lee H. C. , Huh K. B.
Published: December 2004

Aims  First‐degree relatives of patients with Type 2 diabetes mellitus (T2DM) are often reported to be insulin resistant. We wanted to identify early metabolic abnormalities in this condition, and determine whether they are altered by regular physical training.

Methods  We measured insulin sensitivity using the euglycaemic glucose clamp technique and insulin response to oral glucose in 10 unfit (did not participate in routine physical exercise) offspring of T2DM parents and 10 unfit control subjects, and compared them with six fit (routinely swam for 3 h/day 5 days/week) offspring of T2DM parents and six fit controls with no family history of T2DM.

Results  Unfit offspring had a higher plasma glucose response than the other three groups. The mean area under the glucose curve was also significantly higher in unfit offspring than in the other three groups (12.6 ± 0.6 vs. 10.4 ± 0.4, 9.6 ± 0.5, and 9.5 ± 0.7 mmol/l per hour for the unfit controls, fit offspring and fit controls, respectively; P < 0.05). The corresponding insulin response of unfit offspring was significantly higher at 60 min in the oral glucose tolerance test (OGTT) that that of fit offspring or fit controls. In addition, the mean area under the insulin curve was significantly greater in unfit offspring than in either fit offspring or fit controls (868 ± 172 vs. 294 ± 71, 287 ± 43 mmol/l per hour, respectively; P < 0.05). Moreover, the glucose disposal rate (GDR), measured using a euglycaemic clamp, was significantly lower in unfit and fit offspring than in unfit and fit controls (5.6 ± 0.3 vs. 8.6 ± 0.3 mg/kg per minute; P < 0.01 and 9.3 ± 0.9 vs. 12.1 ± 0.8 mg/kg per minute, respectively; P < 0.015), whereas the GDR was similar in unfit controls and fit offspring (8.6 ± 0.4 vs. 9.3 ± 0.9 mg/kg per minute; P > 0.05).

Conclusion  These results support the concept that early metabolic abnormalities, as reflected by a decreased GDR (insulin sensitivity) in the offspring of T2DM patients, may be improved by increased physical fitness.
The long‐term renal and retinal outcome of childhood‐onset Type 1 diabetes
Authors: Harvey J. N. , Allagoa B.
Published: December 2004

Aims  To quantify the influence of childhood onset on long‐term renal and retinal outcome in Type 1 diabetes.

Methods

We used a population‐based diabetes register to identify all Type 1 patients diagnosed before age 15 from 1960 to 1982 and resident in a defined catchment area in 1999. Those diagnosed before age 5, aged 5–9 and 10–14 years were compared with a reference group diagnosed at age 21–25 years over the same period.

Results

Compared with adult‐onset controls, proteinuria occurred earlier (P = 0.02) and nephropathy outcome was worse (P = 0.008) in childhood‐onset diabetes. The risk of developing microalbuminuria was greater in childhood‐onset diabetes: odds ratio 2.6 (95% confidence interval 1.4–4.9, P = 0.003). The relative risk of established nephropathy was 3.8 (1.5–9.4, P = 0.005) with childhood onset. The number developing background retinopathy did not differ with age at onset but younger onset patients were more likely to need laser treatment: relative risk 2.1 (1.1–3.8, P = 0.02). This maintained visual outcome which was not significantly different between the various age at onset groups.

Conclusions

Patients with onset of Type 1 diabetes before age 15 have substantially worse renal outcome and require more laser treatment than adult‐onset patients. Differences between those with onset before age 5, onset at 5–9 and 10–14 years are small compared with the difference between childhood onset and adult onset. Events in the teenage years therefore appear to have a major adverse effect on the risk of developing long‐term microvascular complications.
The Metabolic Syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study
Authors: Bonora E. , Targher G. , Formentini G. , Calcaterra F. , Lombardi S. , Marini F. , Zenari L. , Saggiani F. , Poli M. , Perbellini S. , Raffaelli A. , Gemma L. , Santi L. , Bonadonna R. C. , Muggeo M.
Published: December 2004

Aims  To evaluate the cardiovascular risk associated with the presence of the Metabolic Syndrome in Type 2 diabetic subjects.

Methods  Subjects with the Metabolic Syndrome, defined by WHO criteria, were identified in a large sample of non‐insulin‐treated Type 2 diabetic patients examined within the Verona Diabetes Complications Study (n = 946). At baseline and after a mean of 4.5 years follow‐up, cardiovascular disease (CVD) was assessed by medical history, physical examination, electrocardiogram (ECG) and echo‐duplex of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow‐up were scrutinized in order to identify CVD deaths. In statistical analyses, CVD was considered as an aggregate end‐point, including fatal and non‐fatal coronary, cerebrovascular and peripheral vascular disease as well as ischaemic ECG abnormalities and vascular lesions at the echo‐duplex.

Results  The proportion of subjects with the Metabolic Syndrome was very high (92.3%). At the baseline, 31.7% of subjects were coded positive for CVD, which was more prevalent in subjects with the Metabolic Syndrome (32.9 vs. 17.8%, P = 0.005). Among subjects free of CVD at the baseline (n = 559), CVD events during the follow‐up were significantly increased in patients with the Metabolic Syndrome as compared with those without it (19.9% vs. 3.9%, P < 0.001). Multiple logistic regression analysis showed that, along with sex, age, smoking and HbA1c, the presence of the Metabolic Syndrome independently predicted prevalent (OR 2.01, P = 0.045) and incident CVD (OR 4.89, P = 0.031).

Conclusions  In Type 2 diabetes, the presence of the Metabolic Syndrome is associated with an almost 5‐fold increase in CVD risk.
Regional differences in risk factors and clinical presentation of diabetic foot lesions
Authors: Morbach S. , Lutale J. K. , Viswanathan V. , Möllenberg J. , Ochs H. R. , Rajashekar S. , Ramachandran A. , Abbas Z. G.
Published: December 2004

Background Problems associated with the diabetic foot are worldwide. However, there may be regional variation among risk factors and clinical presentation. Prospective comparative data concerning this topic are rare.

Aim To determine differences in underlying risk factors and clinical presentation of foot problems among people with diabetes in different regions.

Patients and methods Six hundred and thirteen consecutive patients with diabetic foot lesions from three centres [Soest‐Germany (GER), Dar‐es‐Salaam, Tanzania (TAN) and Chennai, India (IND)] were included during the period June 1998 through December 1999. Diabetes‐related data, risk‐factor profiles, and lesion‐related data were collected for each patient. Due to varying proportions of recurrent lesions among the centres, only data from patients with newly presenting diabetic foot lesion were analysed.

Results Of the 613 patients sampled, 368 (60%) were treated for newly presenting diabetic foot lesion. In all three centres, patients were predominately male and had Type 2 diabetes. The average diabetes duration until the onset of the initial foot lesion was 14 years in GER and 12 years in IND, but only 5 years in TAN. The corresponding patient ages were 71, 56 and 51 years. Neuropathy was common to patients in all three centres. Peripheral vascular disease (PVD) was a frequent risk factor in GER (48%). In TAN and IND it was far less common (12 and 13%), probably due to younger patient populations, shorter diabetes duration and lower proportions of smokers. Inadequate footwear was the most common cause of foot lesions in GER (19%), while lack of footwear, irregular foot care and burns were the primary precipitating factors among patients in TAN and IND.

Conclusion Similarities in different regions of the world among people with diabetes suffering newly presenting foot lesions include a predominance of males and patients with Type 2 diabetes, as well as a high frequency of diabetic neuropathy. However, differences concerning age, diabetes duration, peripheral vascular disease, and precipitating factors contributing to injury are also observed.
Facilitating access to glucometer reagents increases blood glucose self‐monitoring frequency and improves glycaemic control: a prospective study in insulin‐treated diabetic patients
Authors: Nyomba B. L. G. , Berard L. , Murphy L. J.
Published: December 2004

Aims  To investigate whether availability of glucometer reagents increases the frequency of self‐blood glucose monitoring (SBGM) and improves glycaemic control in diabetic patients.

Methods  Sixty‐two insulin‐treated diabetic patients were randomized to two groups, matched for age, gender, education, income, type and duration of diabetes, years of insulin treatment, number of daily insulin injections, and haemoglobin (Hb)A1c. All patients were given a glucometer, but one group (no cost, NC) was provided glucometer test strips free of charge. The other group (control, C) had to purchase strips as they found it necessary. Both groups of patients were followed longitudinally at 2‐monthly intervals for 12 months with measurement of blood glucose and HbA1c, and the frequency of SBGM was determined by downloading the glucometer memory.

Results  The SBGM frequency was significantly higher in the NC group vs. the C group during the first 4 months (2.0 ± 0.2 tests/day vs. 1.4 ± 0.1 tests/day, P < 0.025). Mean HbA1c remained stable over the 12 months in the NC group, whereas an increase with time was observed in the C group. The difference in HbA1c between the two groups was significant (P < 0.002) after 6 months. Random blood glucose measured at each visit and average glucose recorded by the glucometer were also lower in the NC group vs. the C group (P < 0.005). There was a negative correlation between HbA1c and SBGM frequency, and HbA1c in patients testing at least twice a day was lower than in those testing less than twice a day (8.8 ± 0.2% vs. 9.6 ± 0.2%, P < 0.001).

Conclusions  In this prospective study, having easy access to glucometer strips provided free of charge to patients increased SBGM frequency. The relationship between HbA1c and SBGM frequency supports the view that SBGM is an essential tool in diabetes management.
Type 2 diabetes in Tirana City, Albania: a rapid increase in a country in transition
Authors: Shapo L. , McKee M. , Coker R. , Ylli A.
Published: December 2004

Aims  To determine how the prevalence of Type 2 diabetes mellitus has changed in Tirana, the capital of Albania, over 20 years.

Methods  Cluster sampling was used to select 700 households including 1540 adults 25 years of age and over in Tirana City, Albania in 2001.

Results  Of 1540 potential subjects, 1120 participated (response rate 72.7%). Using the 1985 WHO criteria to provide comparability with earlier data, the overall prevalence of Type 2 diabetes mellitus in the age group 25+ was 6.3% (95% confidence interval 4.8–7.7); 6.9% (4.8–9.1%) male; 5.6% (3.8–7.5%) female. The age‐adjusted prevalence in those aged 25+ was 5.4%. Of respondents, 3.4% were known to have diabetes, and 2.9% were newly identified through the survey. The prevalence of diabetes increased with age, although among men there was a slight decline after age 65. Impaired glucose tolerance was found in a further 2.9% of respondents, again increasing with age. The prevalence of diabetes has increased significantly since 1980, doubling in the age group 50+. Use of the 1999 WHO diagnostic criteria produces a higher unadjusted prevalence, at 9.7% (8–11.4%). In a logistic regression model, obesity and family history were independent determinants of the probability of having diabetes. Among those known to have diabetes, control was poor.

Conclusions  The prevalence of diabetes in Albania has increased rapidly, consistent with what has been seen in other countries undergoing rapid modernization. It is likely to increase further in the future, with important implications for health policy.
Factors affecting range size differences for plant species on rock outcrops in eastern Australia
Authors: Hunter John T.
Published: December 2004

Abstract: Rock outcrops are considered as habitat or ecological islands discordant from the adjacent matrix. The floras of 24 aggregated outcrop regions within the New England Batholith of eastern Australia were sampled and investigations made into species range differences. A measure is developed to describe differences in species range sizes across floras (range saturation: RS). Range sizes increased in areas with higher incident radiation (higher available energy) and concordantly in regions with a greater proportion of hemi‐parasites, epiphytes and herbs (which were demonstrated to have large range sizes). Differences in species’ range sizes of granite outcrop occurring species on the New England Batholith of eastern Australia at different scales and extents are regressed against selected environmental variables and against local species richness and abundance. Although species’ range size has been linked in a number of systems with increased species richness and local species abundance, such correlations were not obtained in this investigation. Analyses of species’ range sizes could not be used to infer directly on processes that maintain species richness or abundance within the granitic outcrop flora of the New England Batholith.
Vascular Effects of the New Anti-Migraine Agent Almotriptan on Human Cranial and Peripheral Arteries
Authors: Bou J , Gras J , Cortijo J , Morcillo EJ , Llenas J , Palacios JM
Published: December 2004

This paper describes the vascular effects of almotriptan in comparison with sumatriptan in human vessels and tissues in vitro. The contractile properties of almotriptan and sumatriptan were evaluated in vitro in the following arteries: meningeal, temporal, basilar, internal carotid, ophthalmic, pulmonary and coronary. In addition, the effects of almotriptan on the pulmonary vein and on bronchial tissues were studied. Almotriptan showed selectivity of action for migraine-related arteries (i.e. contractile EC50 of 30 and 700 nM for meningeal and temporal arteries, respectively), whereas the effect on arteries supplying blood to the brain was lower. The contractile effect of almotriptan was lower than that of sumatriptan in pulmonary arteries, whereas in bronchial preparations no clinically relevant contractile responses were observed for either almotriptan or sumatriptan. In ophthalmic arteries the contractile effects of almotriptan and sumatriptan were similar, whereas lower contractile effects were obtained with almotriptan than with sumatriptan in coronary arteries.