bluuebunny/crossref_metadata_2025 huggingface dataset:
Addition of rosiglitazone to metformin is most effective in obese, insulin‐resistant patients with type 2 diabetes
Authors: Jones T. A. , Sautter M. , Van Gaal L. F. , Jones N. P.
Published: December 2004

Aim:  These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2DM) taking near‐maximal doses (2.5 g/day) of metformin (MET). In obese, insulin‐resistant patients with T2DM who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue.

Methods:  Data were pooled from two double‐blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2DM patients. Patients were categorized as non‐overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm−2, 25–30 kgm−2, >30 kgm−2 respectively).

Results:  RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta‐cell function were also greatest in the obese patients (4 mg: −16% and +19%; 8 mg: −37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non‐obese.

Conclusions:  In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta‐cell function to a clinically important extent.
Decreasing levels of tumour necrosis factor α and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors
Authors: Samuelsson L. , Gottsäter A. , Lindgärde F.
Published: December 2004

Aim:  Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF‐α), interleukin 6 (IL‐6) and the isoprostane 8‐epi‐prostaglandin (PG) F2α during BMI lowering with orlistat (Xenical®, Roche) or placebo.

Methods:  TNF‐α, IL‐6, and 8‐epi PGF2α evaluated in 376 subjects aged 18–75 years with BMI 28–38 kg/m2 before and after 1 year of double‐blind, randomized treatment with orlistat 120 mg or placebo three times daily.

Results:  Weight reduction was associated with decreasing (p < 0.001) levels of TNF‐α and IL‐6 in both orlistat and placebo groups. After 12 months, TNF‐α was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF‐α correlated with change in s‐glucose (r = 0.22; p = 0.01), and the change in 8‐epi‐PGF2α correlated with changes in s‐cholesterol (r = 0.27; p < 0.001) and s‐LDL‐cholesterol (r = 0.28; p < 0.001).

Conclusion:  Weight reduction was associated with decreasing levels of both TNF‐α and IL‐6. After 12 months of treatment, TNF‐α levels were lower in orlistat than in placebo‐treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.
Cancrum oris in a Caucasian male with Type 2 diabetes mellitus
Authors: Evans L. M. , Lane H. , Jones M. K.
Published: December 2004

We describe a patient with Type 2 diabetes mellitus who developed cancrum oris requiring extensive oro‐facial reconstructive surgery. There are no previous published reports of cancrum oris occurring in a Caucasian subject with no risk factors other than Type 2 diabetes.
Relationship between the severity of retinopathy and progression to photocoagulation in patients with Type 2 diabetes mellitus in the UKPDS (UKPDS 52)
Authors: Group Uk Prospective Diabetes Study (ukpds) , Kohner E. M. , Stratton I. M. , Aldington S. J. , Holman R. R. , Matthews D. R.
Published: December 2004

Aim  to establish the degree to which the severity of retinopathy determines the risk for the need for subsequent photocoagulation in those with newly diagnosed Type 2 diabetes mellitus.

Methods  Of 5102 patients entered into the UK Prospective Diabetes Study (UKPDS), 3709 had good quality retinal photographs that could be graded at entry. They were followed until the end of the study or until lost to follow‐up, or until they received photocoagulation. Retinopathy severity was categorized as no retinopathy, microaneurysms (MA) only in one eye, MA in both eyes or more severe retinopathy features. The risk of photocoagulation was assessed in relation to severity of retinopathy at baseline, 3 and 6 years.

Results  Of the 3709 patients assessed at entry to the UKPDS, 2316 had no retinopathy. Of these 0.2% needed photocoagulation at 3 years, 1.1% at 6 years and 2.6% at 9 years. Those with MA in one eye only (n = 708) were similar, with 0%, 1.9% and 4.7% needing photocoagulation by 3, 6 and 9 years, respectively. Amongst those who had more retinopathy features at entry (n = 509), 15.3% required photocoagulation by 3 years, and 31.9% by 9 years. When those without retinopathy at 6 years (n = 1579) were examined 3 and 6 years later (9 and 12 years after diagnosis), 0.1% and 1.8% required photocoagulation. Those with more severe retinopathy (n = 775) needed earlier treatment, 6.6% after 3 years and 13.3% after 9 years. The commonest indication for laser therapy was maculopathy, but those with more severe retinopathy were more likely to be treated for proliferative retinopathy and to need both eyes treated.

Conclusion  Few type 2 diabetic patients without retinopathy progress to photocoagulation in the following 3–6 years, while patients with more severe retinopathy lesions need to be monitored closely.
The effect of diabetes and severe ischaemia on the penetration of ceftazidime into tissues of the limb
Authors: Raymakers J. T. , Houben A. J. , Heyden J. J. vd , Tordoir J. H. , Kitslaar P. J. , Schaper N. C.
Published: December 2004

SUMMARY

Aims  To determine the effect of diabetes and of different degrees of ischaemia on the penetration of ceftazidime into different tissues.

Methods  Sixteen patients (10 with diabetes mellitus) undergoing lower extremity amputation for severe ischaemia (in 12 in combination with infection), received 2000 mg ceftazidime intravenously as a bolus 30 min prior to the operation. Skin perfusion was determined by transcutaneous oxygen pressure measurements (TcPO2) on the dorsal side of the midfoot. After amputation bone, skin and muscle samples were obtained from the forefoot, midfoot and proximal tibia. Tissue and plasma concentrations were determined by HPLC. The tissue concentrations were corrected for blood contamination.

Results  No differences were observed in skin, muscle or bone ceftazidime levels between diabetic and non‐diabetic patients. Multiple regression analysis suggested that tissue perfusion was a major determinant of skin and bone ceftazidime concentrations, predicting 40–47% of the ceftazidime concentrations at several biopsy sites.

Conclusions  The present study suggests that tissue perfusion is the major determinant of the penetration of a third generation cephalosporin into the tissues of the ischaemic (diabetic) foot. Diabetes alone however, has no major effects upon this penetration.
Coeliac disease and Type 1 diabetes mellitus – the case for screening
Authors: Holmes G. K. T.
Published: December 2004

SUMMARY

Aim  To review the relationship between coeliac disease and Type 1 diabetes mellitus with emphasis on prevalence of coeliac disease, presentation and implications for screening.

Methods  Papers collected over many years by the author have been included in the review and a literature search employing Medline was undertaken to August 2000. Search words used were coeliac disease and diabetes mellitus.

Results  Twenty papers exploring the prevalence of coeliac disease by serological screening of Type 1 diabetes in children, eight in adults and two including both groups were found. An additional 48 papers are included and relate to serological screening tests for coeliac disease, expressions and complications of coeliac disease, the value of GFD and the genetics of the two conditions. Unless formal screening studies are undertaken coeliac disease will not be diagnosed because patients are asymptomatic, have atypical symptoms or even in those with symptoms the diagnosis is overlooked. Based on small bowel biopsy, diagnosis the prevalence of coeliac disease in Type 1 diabetes in children is 1:6 to 1:103 and in adults 1:16 to 1:76. Patients may improve following the start of a gluten‐free diet (GFD) in terms of symptoms, growth in children, serum antibody levels, haematological and biochemical indices, morphology of the small intestinal mucosa and control of diabetes.

Conclusion  Coeliac disease commonly occurs in Type 1 diabetes. It is recommended that screening for coeliac disease should be part of the routine investigation and offered to all patients because of the high prevalence and the potential benefits of treatment with a GFD. This includes control of symptoms, stabilization of diabetes and prevention of complications associated with coeliac disease. The cost per patient diagnosed with coeliac disease from the existing population with Type 1 diabetes would be £860 and for those newly arising £950.
Prevalence and awareness of diabetes and mean fasting glucose by age, sex, and region: results from the Nutrition and Health Survey in Taiwan, 1993–1996
Authors: Pan W.‐H. , Yeh W.‐T. , Chang H.‐Y. , Hwu C.‐M. , Ho L.‐T.
Published: December 2004

Aims The objective of this study was to evaluate the prevalence and awareness of diabetes mellitus (DM) in Taiwan.

Methods The Nutrition and Health Survey in Taiwan for people aged ≥ 4 years was conducted between 1993 and 1996, using a multistaged, stratified, and clustered sampling scheme.

Results The prevalence of DM, defined by fasting whole blood glucose ≥ 6.1 mmol/l or diagnosed DM subjects taking hypoglycaemic drugs, was 3.7% in men ≥ 19 years and 6.3% in women. Corresponding to age groups 19–44, 45–64 and ≥ 65 years, the prevalence was 1.5%, 7.9% and 7.8% in men and 0.5%, 12.3% and 19.6% in women, respectively. People in mountainous areas and in Peng‐Hu islands had the highest prevalence, but the lowest awareness rates among seven survey strata (regions). Women from metropolitan cities had the lowest DM prevalence and body mass index (BMI) values, but the highest rate of DM awareness among all strata. This phenomenon was not apparent in men. The age, sex, and regional patterns of DM prevalence were consistent with those of BMI.

Conclusions The prevalence of DM in Taiwan in 1993–1996 was relatively high, given a mean BMI of 23 kg/m2 in adults. Gender and regional differences were apparent in DM prevalence and awareness and in mean BMI.

Diabet. Med. 20, 182–185 (2003)
Perceived risk for Type 2 diabetes in participants in a stepwise population‐screening programme
Authors: Adriaanse M. C. , Snoek F. J. , Dekker J. M. , Spijkerman A. M. W. , Nijpels G. , Van Der Ploeg H. M. , Heine R. J.
Published: December 2004

Aims To determine the risk perception of Type 2 diabetes in participants in a stepwise population‐screening programme.

Methods This study was carried out within the framework of a stepwise Type 2 diabetes population screening in the general (age 50–75 years) Dutch population. Main outcome measures were perceived risk of having diabetes and perceived seriousness of diabetes, based on a self‐report questionnaire, completed before being informed about the diagnosis (Type 2 diabetes yes/no) of the screening procedure. Among 7736 participants, the risk perception of 217 screening‐detected participants was compared with 4435 with a low‐risk profile for undiagnosed Type 2 diabetes.

Results Of 7736 participants, 43.5% could not give an estimate of their risk of having diabetes, 31.2% estimated their risk to be 0% and 25.3% estimated their risk to be 10% or higher. Compared with 4435 participants with an objectively low risk profile, 217 screening‐detected participants were more likely to answer ‘I do not know’ (52.4% vs. 40.1%, P < 0.001), perceived their risk less often to be 0% (19.3% vs. 34.7%, P < 0.001), and slightly more often perceived their risk to be 10% or higher (28.3% vs. 25.2%, P < 0.001). Overall, more than half of the total population, including both participants with a low risk profile and the screening‐detected participants, perceived diabetes as a (very) serious disease. Higher age, obesity and taking anti‐hypertensive drugs did not translate into a higher perceived risk.

Conclusions Among screening‐detected participants the seriousness of Type 2 diabetes was generally acknowledged, whilst the perceived risk of having Type 2 diabetes was low, despite the presence of risk factors.

Diabet. Med. 20, 210–215 (2003)
Hypertension, anti‐hypertensive drug therapy and erectile dysfunction in diabetes
Authors: Moulik P. K. , Hardy K. J.
Published: December 2004

Aims Erectile dysfunction (ED) is common in diabetes and may be related to the high prevalence of hypertension and consequent anti‐hypertensive drug therapy in diabetic patients. The risk factors for ED were studied with particular reference to hypertension and anti‐hypertensive drugs.

Methods We performed a retrospective case note analysis of 763 consecutive male patients (34% Type 1 diabetes, 65% Type 2 diabetes) attending an adult diabetic clinic to collect data on risk factors for ED. We specifically recorded the use of anti‐hypertensive drugs.

Results Two hundred and ninety‐nine (39%) patients had ED. Mean age of patients with ED (61 years) was higher than those without (mean age 51 years, P < 0.001). The mean age of hypertensive patients was also significantly higher than those without. On multivariate regression analysis, age (P < 0.001), macrovascular disease (P < 0.001), sensorimotor neuropathy (P < 0.001) and HbA1c (P < 0.05) predicted ED. Neither hypertension nor any anti‐hypertensive medication independently predicted ED.

Conclusion Our data suggest that ED in diabetic patients with hypertension may be related to the higher age and prevalence of macrovascular disease rather than hypertension or its treatment.
The relationship between the circulating IGF system and the presence of retinopathy in Type 1 diabetic patients
Authors: Frystyk J. , Bek T. , Flyvbjerg A. , Skjærbæk C. , Ørskov H.
Published: December 2004

Background Patients with proliferative diabetic retinopathy (PDR) have increased vitreous levels of insulin‐like growth factor (IGF)‐I, IGF‐II and IGF binding proteins (IGFBPs). This accumulation is probably caused by increased leakiness of the blood–retina barrier and influx of circulating IGFs and IGFBPs. To date, interest has focused on the role of circulating total IGF‐I in the development of PDR, and there are only sparse data on circulating levels of free IGF‐I and IGFBPs.

Methods We compared fasting serum samples from matched groups of Type 1 diabetic patients with no retinopathy (n = 29), non‐PDR (n = 13) and PDR (n = 16). We also included matched controls (n = 26). Serum was analysed for free and total IGF‐I and ‐II, free plus dissociable IGF‐I, IGFBP‐1, ‐2 and ‐3, IGFBP‐1‐bound IGF‐I as well as IGFBP‐3 proteolysis.

Results When compared with controls, diabetic patients (n = 58) showed reduced (P < 0.0005) levels of free and total IGFs, free plus dissociable IGF‐I and IGFBP‐3, whereas levels of IGFBP‐1, IGFBP‐1‐bound IGF‐I and IGFBP‐2 were elevated. IGFBP‐3 proteolysis remained unaltered. When comparing diabetic patients with different degrees of retinopathy, IGFBP‐2 and IGFBP‐1‐bound IGF‐I were the only parameters that differed significantly. Patients with retinopathy (non‐PDR as well as PDR) had elevated IGFBP‐2 (P < 0.03) and reduced IGFBP‐1‐bound IGF‐I (P < 0.03), when compared with patients without retinopathy. Noteworthy, both parameters correlated (0.11 < r2 < 0.14, P < 0.02) with the severity of retinopathy.

Conclusion Our study gives no evidence of a direct role of circulating free IGF‐I in the development of PDR, whereas IGFBP‐2 and IGFBP‐1‐bound IGF‐I showed a relationship with the degree of retinopathy. However, further investigations are needed in order to clarify the basis and clinical relevance of this finding.
Alternate site blood glucose testing: do patients prefer it?
Authors: Tieszen K. L. , New J. P.
Published: December 2004

Aims To examine patients’ perspectives on ease of use and pain with the MediSense alternate site blood glucose testing device (Soft‐Sense) compared with their current glucose testing method, and to evaluate the analytical performance of the MediSense device with the laboratory reference method.

Methods Study participants were shown how to use the Soft‐Sense glucose device and asked to perform two tests on their forearm. A capillary sample was collected from their finger and tested on the external port of the Soft‐Sense meter and a laboratory method (YSI Glucose Analyser). Finally, one drop of blood was also directly tested from the finger onto the external port. Patients completed a questionnaire comparing ease of use and associated pain of their current testing method with the Soft‐Sense meter.

Results Patients preferred the Soft‐Sense device to their own for ease of use and for less pain (93% found it easier to use and 96% less painful; P < 0.001). Glucose results correlated closely with the laboratory method (mean absolute percentage bias for the forearm 11.0%, finger 6.0%, and collected capillary sample 5.7%). Error grid analysis showed that all Soft‐Sense results were clinically acceptable.

Conclusions Patients prefer the Soft‐Sense alternate site testing device to their existing measuring method. The device accurately measures whole blood glucose.
Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy
Authors: Yuyun M. F. , Dinneen S. F. , Edwards O. M. , Wood E. , Wareham N. J.
Published: December 2004

Aims To determine the nature of the association between baseline albuminuria and risk of all‐cause mortality and cardiovascular disease, and to determine if the rate of change of albuminuria from baseline over 1 year predicts these endpoints in patients with diabetic nephropathy.

Methods Cohort study of 427 patients (161 Type 1 and 266 Type 2) with diabetic nephropathy defined as urinary albumin excretion (UAE) ≥ 30 mg/24 h at baseline (mean age 53.4 years). Patients were recruited at the time of referral to a diabetic nephropathy clinic and followed up annually for an average of 5 years. UAE rate was re‐measured at 1 year and the rate of change from baseline calculated.

Results All‐cause mortality and cardiovascular disease increased significantly and continuously across quintiles of baseline UAE (P for linear trend < 0.001 in both outcomes). The rate of change of albuminuria over 1 year (log10) independently predicted all‐cause mortality (hazard ratio (95% confidence interval) 1.76 (1.39, 3.11)) and cardiovascular mortality (1.57 (1.13, 5.22)). Taken as a categorical variable, a rate of change of albuminuria ≥ 30% independently predicted mortality and cardiovascular events (2.07 (1.5, 4.30) and 1.89 (1.33, 4.06), respectively).

Conclusions The rate of change of albuminuria over 1 year independently predicts mortality and cardiovascular disease in diabetic nephropathy and may have clinical utility as a risk marker in identifying a subgroup of patients at particular risk. The risk of these outcomes is continuous across the range of baseline albuminuria in patients with diabetic nephropathy.
Type 2 diabetes presenting as diabetic ketoacidosis in adolescence
Authors: Valabhji J. , Watson M. , Cox J. , Poulter C. , Elwig C. , Elkeles R. S.
Published: December 2004

We report two black adolescent subjects who presented with diabetic ketoacidosis, but who lacked autoimmune markers and demonstrated clinical and biochemical characteristics more typical of Type 2 diabetes, including obesity, acanthosis nigricans, positive family history for Type 2 diabetes, and Type 2 diabetic dyslipidaemia. Subsequent to acute presentation, insulin was discontinued in both subjects and excellent glycaemic control was achieved with metformin therapy alone. Four months following acute presentation, both had adequate C‐peptide responses to intravenous glucagon. Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects.

Diabet. Med. 20, 416–417 (2003)
Amniotic fluid insulin levels and fetal abdominal circumference at time of amniocentesis in pregnancies with diabetes
Authors: Schaefer‐Graf U. M. , Kjos S. L. , Bühling K. J. , Henrich W. , Brauer M. , Heinze T. , Dudenhausen J. W. , Vetter K.
Published: December 2004

Aims Fetal hyperinsulinism is a strong predictor for excessive growth and fetopathy in pregnancies complicated by diabetes. We examined (i) the relationship between measurements of amniotic fluid insulin (AF insulin) and fetal abdominal circumference (AC) at the time of amniocentesis, and (ii) whether there is a threshold for fetal AC percentiles which can identify low vs. high‐risk levels of AF insulin without performing an amniocentesis.

Methods In a retrospective study, AF insulin from 121 pregnant diabetic women (32 pregestational; 89 gestational) was measured during the 3rd trimester as part of a diabetes management protocol. AC measurements were transformed into a continuous variable of percentile growth for gestational age (Hadlock). Division of the cohort according to deciles or quartiles of AC percentiles was performed to identify a threshold AC with a significant increase in elevated AF insulin, previously defined as AF insulin ≥ 7 µU/ml. A receiver operator characteristic (ROC) curve was created and the negative predictive value (NPV) of the determined threshold was calculated.

Results AF insulin levels were significantly correlated with the AC percentiles (r = 0.3, P = 0.0005) by linear regression. No AC threshold could reliably identify a moderate elevated AF insulin ≥ 7 µU/ml (NPV 77.2%), but an AC threshold ≥ 75th percentile could identify with fetal hyperinsulinism with an AF insulin ≥ 16 µU/ml. All 10 cases of AF insulin ≥ 16 µU/ml were identified with a NPV of 100% (74/74).

Conclusions Our data indicate that an AC ≥ 75th percentile determined by a 3rd trimester ultrasound examination may discriminate between pregnancies at low vs. high risk for AF insulin ≥ 16 µU/ml. This AF insulin concentration corresponds to a level of hyperinsulinism reported to be associated with considerable neonatal and long term morbidity.

Diabet. Med. 20, 349–354 (2003)
Plasma N‐terminal pro‐brain natriuretic peptide in Type 1 diabetic patients with and without diabetic nephropathy
Authors: Siebenhofer A. , Ng L. L. , Plank J. , Berghold A. , Hödl R. , Pieber T. R.
Published: December 2004

Aims Plasma N‐terminal pro‐brain natriuretic peptide (NT proBNP) is produced and released from cardiac ventricles; it is elevated in patients with heart failure, hypertension and chronic renal failure. This study aimed to examine the plasma levels of NT proBNP and their relationship in Type 1 diabetic patients with and without diabetic nephropathy.

Methods We developed a non‐competitive immunoluminometric assay with in‐house antibodies to the N‐ and C‐terminal domains of NT proBNP. We compared NT proBNP levels between 47 normoalbuminuric patients (group 1), 12 microalbuminuric patients (group 2) and 12 patients with macroalbuminuria (group 3).

Results There were significant differences in 24‐h systolic and diastolic blood pressure, diabetes duration, serum creatinine, LDL‐cholesterol and HbA1c between the three groups; other parameters did not differ significantly. NT proBNP (median and range) levels were 5 (0.75–68), 22 (0.75–82) and 23 (0.75–374) fmol/ml for groups 1–3, respectively. Log‐transformed data of NT proBNP were used to compare all three groups (P = 0.016). The Pearson correlation between NT proBNP and albuminuria (R = 0.27; P = 0.02) was positive; HbA1c (R = 0.25; P = 0.03) and age (R = 0.33; P = 0.005) correlated significantly as well. On the basis of multiple regression analysis, the adjusted difference remained significant between the three groups.

Conclusions This is the first demonstration that NT proBNP levels are significantly higher in Type 1 diabetic patients with albuminuria. This may be caused by a down‐regulation of A‐type guanylate cyclase‐coupled natriuretic peptide receptors in renal tubules or by elevated NT proBNP levels leading to higher glomerular hydraulic pressure or higher capillary permeability and possibly increased albumin excretion. Further studies are required to investigate the potential role of NT proBNP in patients with diabetic nephropathy and such other co‐morbidities as cardiovascular disease.

Diabet. Med. 20, 535–539 (2003)
Continuous glucose monitoring for treatment adjustment in diabetic pregnancies—a pilot study
Authors: Yogev Y. , Ben‐Haroush A. , Chen R. , Kaplan B. , Phillip M. , Hod M.
Published: December 2004

Aims To examine the efficacy of a continuous glucose monitoring (CGM) system for treatment adjustment in patients with diabetic pregnancy treated with insulin.

Methods The study sample consisted of eight women with diabetic pregnancy, six with pre‐pregnancy Type 1 diabetes mellitus and two with gestational diabetes (GDM), all being treated with multiple daily insulin injections. Gestational age ranged from 24 to 32 weeks. Data derived from the Continuous Glucose Monitoring System (MiniMed) for 72 h were compared with fingerstick glucose measurements (six to eight times a day), and treatment was adjusted on the basis of the findings. Two to four weeks later, the patients were re‐evaluated with CGM.

Results In the first part of the study, an average of 744 ± 33 glucose measurements was recorded for each patient with CGM. The mean total time of hyperglycaemia (glucose level > 7.7 mmol/l) undetected by the fingerstick method was 152 ± 33 min/day. Nocturnal hypoglycaemic events (glucose level < 2.7 mmol/l) were recorded in seven patients. Based on the additional information obtained by continuous monitoring, the insulin regimen was changed in all patients. CGM re‐evaluation after treatment adjustment showed a reduction in undetected hyperglycaemia to 89 ± 17 min/day and in nocturnal hypoglycaemic events, which were recorded in only one patient.

Conclusions Continuous glucose monitoring may diagnose high blood glucose levels and nocturnal hypoglycaemic events that are unrecognized by intermittent blood glucose monitoring and could serve as a useful tool for the long‐term management of diabetic pregnancies. A large prospective study is needed to determine the clinical implications of this new monitoring technique.

Diabet. Med. 20, 558–562 (2003)
Respiratory failure secondary to diabetic neuropathy affecting the phrenic nerve
Authors: Tang E. W. , Jardine D. L. , Rodins K. , Evans J.
Published: December 2004

We report a patient with Type 2 diabetes mellitus complicated by neuropathy affecting the phrenic nerves, resulting in fatal respiratory failure. Diabetic mononeuropathy is common and usually recovers spontaneously, but bilateral phrenic nerve involvement appears to be uncommon and difficult to treat. The pathology of diabetic mononeuropathy is not well understood and we believe this to be the first histological report of a phrenic nerve biopsy in this condition.

Diabet. Med. 20, 599–601 (2003)
Type 2 diabetes mellitus: a disease of the innate immune system? An update
Authors: Crook M.
Published: December 2004

A few years ago a hypothesis was proposed suggesting that elements of the innate immune system, such as acute phase reactants, contribute to the development of Type 2 diabetes mellitus. Acute phase reactants such as C‐reactive protein and sialic acid may thus predict risk of developing Type 2 diabetes mellitus, as well as being markers of diabetes microvascular and macrovascular complications. This article discusses these issues.
Body composition in adolescent girls with Type 1 diabetes
Authors: Ingberg C‐M. , Särnblad S. , Palmér M. , Schvarcz E. , Berne C. , Åman J.
Published: December 2004

Aims  To compare body composition in adolescent girls with Type 1 diabetes with healthy controls.

Research design and methods  In this population‐based study, body composition was examined, using dual‐energy X‐ray absorptiometry (DXA) and skinfold measurements, in 18 adolescent post‐menarcheal females, 16–19 years of age, with Type 1 diabetes since childhood in comparison to age‐matched healthy control subjects.

Results  Body mass index was 2.7 kg/m2 higher in diabetic patients (26.3 ± 2.6 vs. 23.6 ± 3.8; P < 0.05). The overweight consisted almost entirely of increased fat mass, as evaluated by both skinfold measurements and DXA. Bone mineral density did not differ between the two groups. In diabetic females, the distribution of the fat mass was increased in the upper part of the body. The fat distribution, expressed as the abdominal‐to‐leg ratio, was significantly correlated to glycated haemoglobin (HbA1c) (r = 0.69; P < 0.005), daily dosage of insulin expressed per kilogram body weight (r = 0.78; P < 0.0005) and total cholesterol (r = 0.60; P < 0.001).

Conclusions  The observed overweight in adolescent females with Type 1 diabetes is explained by an increased fat mass. Abdominal fat accumulation was associated with poor glycaemic control, increased need for insulin and elevated blood lipids.

Diabet. Med. **, ***–*** (2003)
Diabetes‐related inequalities in health status and financial barriers to health care access in a population‐based study
Authors: Gulliford M. C. , Mahabir D. , Rocke B.
Published: December 2004

Aims  We evaluated the relationship between diabetes, health status, household income and expenditure on health care in the general population in Trinidad.

Methods  Multistage sampling of 300 households was used to select a sample of 548 adults aged ≥ 25 years. There were 64 (12%) who reported a diagnosis of diabetes. Comparison was made with 128 non‐diabetic controls who were frequency matched for age and sex.

Results  Subjects with diabetes had lower income levels than non‐diabetic controls [income ≤ US$533 per month for 66% diabetes cases and 48% controls, test for trend P = 0.007]. Compared with controls, subjects with diabetes were less likely to have good or very good self‐rated health (diabetes 32%, controls 67%; P < 0.001), and more frequently reported long‐standing illness, limitation of activities, visual impairment, or self‐reported history of high blood pressure, angina or heart attack. Subjects with diabetes (11%) were less likely than controls (30%) to have private health insurance (P = 0.005). Diabetic subjects (35%) were more likely than controls (16%) to have incurred expenditure on doctors’ services in the last 4 weeks (P = 0.021).

Conclusions  Diabetes is associated with worse health status and more frequent expenditure on medical services but greater financial barriers to access in terms of low income and lack of health insurance. Policies for diabetes should specifically address the problem of income‐related variations in risk of diabetes, health care needs and barriers to uptake of preventive and treatment services, otherwise inequalities in health from this condition may increase.
Association between smoking, insulin resistance and β‐cell function in a North‐western First Nation
Authors: Daniel M. , Cargo M. D.
Published: December 2004

Aims  Aboriginal peoples have a high prevalence of smoking and are at major risk for diabetes. The role of insulin resistance vs. compromised β‐cell function in the link between smoking and glycaemic disease is not clear. This study tested whether relations between insulin resistance and β‐cell function differ between current smokers, former smokers and non‐smokers, and if having diabetes modifies smoking‐related effects.

Methods  A community‐based diabetes screening initiative was mounted for a North‐western First Nation (Interior Salishan) in rural British Columbia, Canada. Respondents were on‐reserve Aboriginal people (n = 156), all adults 18 + years. Glycaemic status was determined by oral glucose tolerance test. Fasting values for glucose and insulin were used to estimate β‐cell function and insulin resistance by homeostasis model assessment (HOMA). Analyses adjusted for age, sex, alcohol intake, education, body mass index and physical activity.

Results  For normoglycaemic persons (n = 119) current smokers relative to non‐smokers had high β‐cell values [difference (95% confidence interval) 19.5 (17.1, 21.9)], while former smokers had low β‐cell values [difference −22.8 (−20.3, −25.3)] (P < 0.0001). For diabetic persons (n = 37) differences were of equivalent direction but greater magnitude (P < 0.0001). Insulin resistance was for normoglycaemic persons highest for current smokers, and for diabetic persons lowest for current smokers (P = 0.021).

Conclusions  Former smoking is associated with low β‐cell function, and current smoking with high β‐cell function, independent of diabetes in the North‐western First Nation surveyed. Associations between smoking and insulin resistance vary according to glycaemic status. Smoking may have diametric acute and post‐cessation effects on β‐cell function and insulin resistance.
Diabetes control and complications: the role of glycated haemoglobin, 25 years on
Authors: Jeffcoate S. L.
Published: December 2004

The long‐term complications of diabetes have major consequences for individual subjects and growing healthcare delivery and cost implications for society. Evidence for the benefits of good glycaemic control, as monitored by glycated haemoglobin measurements, has been developed in the 25 years since they were introduced to the point where HbA1c assays play central roles in patient management, clinical guidance and audit, and clinical trial design. In this review this evidence is examined and three classes of uncertainty identified that diminish confidence in the effectiveness of these roles for HbA1c.

Analytical variability between different methods for HbA1c has restricted the application of clinical targets and this problem has recently been addressed by reference method standardization. There are two approaches to this which result in different HbA1c values and this discrepancy needs to be resolved.

Biological variability in HbA1c values between individuals also restricts its predictive role when applied to populations. The correlations between HbA1c measurements and various components of glycaemia (overall, fasting, postprandial) are still uncertain and differences in protein glycation and de‐glycation are greater between subjects than often thought. The influence of variability in erythrocyte life span is an area where research is needed, especially in diabetic subjects.

Clinical variability is the most important and complex area of uncertainty. A predictive link between HbA1c and clinical outcomes is not as clear‐cut as often stated. The correlation with the development of microvascular disease is well established in Type 1 diabetes, but in Type 2 subjects (90% of those with diabetes) the evidence that HbA1c monitoring is of value in predicting or preventing macrovascular disease is not strong, although it is the major cause of morbidity and early death in this group.

It is recommended that, as a matter of urgency, these issues be examined, particularly within the context of self‐care in diabetes.

Diabet. Med. **, ***–*** (2003)
Association between fasting glucose and C‐reactive protein in middle‐aged subjects
Authors: Aronson D. , Bartha P. , Zinder O. , Kerner A. , Shitman E. , Markiewicz W. , Brook G. J. , Levy Y.
Published: December 2004

Aims  C‐reactive protein (CRP), a marker of subclinical inflammation, predicts the occurrence of coronary heart disease in healthy subjects. Hyperglycaemia is known to stimulate the release of inflammatory cytokines from various cell types and can lead to the induction and secretion of acute‐phase reactants by adipocytes. The aim of the present study was to determine the relation between glycaemic status and CRP in healthy subjects.

Methods  We studied the relation of high‐sensitivity CRP to fasting glucose and other components of the metabolic syndrome in a population‐based cross‐sectional study (n = 1000; age 50 ± 9 years).

Results  Plasma CRP levels increased continuously from the lowest quartile of normal fasting glucose level to impaired fasting glucose and to diabetes (ln CRP 0.47 ± 0.09, 0.95 ± 0.12, and 1.11 ± 0.13, respectively; Ptrend < 0.0001). Increasing CRP with higher fasting glucose levels was apparent even among subjects with fasting glucose in the normal range (Ptrend = 0.039), and subjects with fasting glucose level in the upper quartile of normal fasting glucose had higher CRP levels compared with subjects in the lower quartile (P = 0.035). There was a positive crude correlation between CRP and smoking, post‐menopausal hormone use, body mass index, fasting glucose, triglycerides, hypertension, and uric acid (r = 0.11–0.36, P = 0.002–0.0001). A negative correlation was found between CRP and HDL‐cholesterol (r = 0.12, P < 0.0001) and physical activity (r = 0.11, P = 0.002). After adjustment for potential confounders in a stepwise multivariate linear regression model, fasting glucose remained significantly and independently related to CRP levels (correlation coefficient 0.06; 95% confidence interval 0.014–0.11, P = 0.011).

Conclusions  Fasting glucose is significantly and positively associated with plasma CRP in middle‐aged subjects. CRP levels increase continuously across the spectrum of fasting glucose, beginning in the lowest quartile of normal fasting glucose. This finding suggests that a proinflammatory effect may contribute to the adverse cardiovascular outcome associated with diabetes, impaired fasting glucose, and increasing glucose levels within the normal range.
Evidence for linkage on chromosome 4p16.1 in Type 1 diabetes Danish families and complete mutation scanning of the WFS1 (Wolframin) gene
Authors: Larsen Z. M. , Johannesen J. , Kristiansen O. P. , Nerup J. , Pociot F. ,   The Danish IDDM Epidemiology and Genetics Group and The Danish Study Group of IDDM in Childhood
Published: December 2004

Aims  To investigate whether the WFS1 gene, the gene for Wolfram syndrome, is a susceptibility gene for more common forms of diabetes in the Danish population.

Methods  One hundred and fifty‐two Danish Type 1 diabetes mellitus sib‐pair families were genotyped for two microsatellite markers situated within 5 cM of the WFS1 gene and analysed for linkage and association using the sib‐TDT. The entire coding region, the 5′UTR and 3′UTR of the WFS1 gene, were screened for mutations by direct sequencing in 29 selected Type 1 diabetes patients. Four of the identified mutations were tested for linkage and association in 255 Danish Type 1 diabetes families (including 103 simplex families).

Results  Evidence for linkage to Type 1 diabetes was found as the second most frequent allele of the marker D4S394 were transmitted 137 times (T = 61%) and not transmitted 88 times to affected offspring (Puc = 0.0011). Twelve mutations were found in the coding region and three mutations in the 3′UTR. No evidence for linkage and association to Type 1 diabetes was found testing four of the identified amino acid substitutions.

Conclusions  Evidence of linkage to Type 1 diabetes was observed in the Danish family collection. However, no evidence of linkage and association was observed for any of the analysed polymorphisms, suggesting that other variations must be responsible for the observed evidence of linkage in the region.

Diabet. Med. 20, ***–*** (2003)
Nine weeks of bedtime diazoxide is well tolerated and improves β‐cell function in subjects with Type 2 diabetes
Authors: Qvigstad E. , Kollind M. , Grill V.
Published: December 2004

Aims  To test whether a bedtime dose of diazoxide can improve daytime β‐cell function without side‐effects in Type 2 diabetes.

Methods  A double‐blind randomized study was performed in 27 Type 2 diabetic subjects (17 male, 10 female) who were treated with bedtime insulin and metformin. Subjects received either bedtime diazoxide, 100 mg, or placebo for 9 weeks. Duplicate C‐peptide glucagon tests were performed before and in the last days of intervention.

Results  No side‐effects of diazoxide were detected. Treatment with diazoxide did not incur any increase in bedtime insulin. C‐peptide responses to glucagon tended to increase: 0.15 ± 0.06 nmol/l vs. −0.01 ± 0.04 nmol/l for placebo, P < 0.06 for difference. Corresponding effects on insulin were 66.2 ± 41.7 pmol/l for diazoxide vs. −84.2 ± 51.5 for placebo, P < 0.03. Treatment with diazoxide decreased fasting glucagon levels by 41% vs. placebo, P < 0.03. Glycated haemoglobin (HbA1c) levels were not affected, whereas levels of blood glucose post breakfast were higher during diazoxide (1.34 ± 0.43 mmol/l, P < 0.01 vs. placebo).

Conclusions  Bedtime treatment with diazoxide in Type 2 diabetic subjects on bedtime insulin and metformin has no significant side‐effects, does not increase bedtime insulin supplementation, tends to ameliorate β‐cell function but fails to improve metabolic control.
Street drug use among young patients with Type 1 diabetes in the UK
Authors: Ng R. S. H. , Darko D. A. , Hillson R. M.
Published: December 2004

Background  Diabetic ketoacidosis (DKA) and poor glycaemic control in young adults with Type 1 diabetes may be associated with street drug use. There are few studies in the UK looking at the prevalence of drug use in young adults with diabetes.

Methods  One hundred and fifty‐eight young adults, aged sixteen to thirty years, with Type 1 diabetes attending an urban diabetes clinic were sent an anonymous confidential postal questionnaire to determine the prevalence of street drug use.

Results  We received 85 completed responses. Twenty‐nine percent of respondents admitted to using street drugs. Of those, 68 percent habitually took street drugs more than once a month. Seventy‐two percent of users were unaware of the adverse effects on diabetes.

Interpretation  Self‐reported street drug usage in young adults with Type 1 diabetes is common and may contribute to poor glycaemic control and serious complications of diabetes.
Modular Headache Theory
Authors: Young WB , Peres MFP , Rozen TD
Published: December 2004

Many people experience headaches that do not fulfil the International Headache Society's criteria for a specific headache disorder yet behave biologically like that disorder. Others fulfil criteria for one headache disorder and yet have features of another disorder. To explain these observations, we propose that groups of neurones called modules become activated to produce each symptom of a primary headache disorder, and that each module is linked to other modules that together produce an individual's headache. This theory has implications for the classification, research and treatment of primary and secondary headache patients.
The Validity of ‘Recognition-Based’ Headache Diagnoses in Adolescents. Data from the Nord-TrØndelag Health Study 1995-97, Head-Hunt-Youth
Authors: Zwart J-A , Dyb G , Stovner LJ , Sand T , Holmen TL
Published: December 2004

The aim of this study was to evaluate the validity of the headache diagnoses (migraine and tension-type headache) obtained from short interviews by nurses, where the subjects were asked to identify their headache(s) based on recognition of typical headache descriptions. All students in junior high schools and high schools aged 12-19 years in Nord-Tr⊘ndelag county, Norway, were invited to participate in the youth part of the Nord-Tr⊘ndelag Health Study ('Helseunders⊘kelsen i Nord-Tr⊘ndelag'-HUNT), 1995-1997. In this cross-sectional study a total of 8984 students (88%) completed a comprehensive questionnaire with different health-related items. Of these, 6149 were also interviewed by nurses about their headache complaints by giving them two alternative headache descriptions accordant with either migraine or tension-type headache (Head-HUNT-Youth). The headache diagnoses obtained from nurse interviews were validated in a stratified random sample enriched with headache subjects from the interviewed population. Out of 159 invited individuals, 112 (70%) participated in extensive semistructured interviews by neurologists. The overall chance-corrected agreement (K) was 0.76 (confidence interval (CI) 0.66-0.86), which is considered good. For migraine, the positive and negative predictive values were 89% and 90%, respectively, and the chance-corrected agreement (K) was 0.72 (CI 0.58-0.87). For tension-type headache, positive and negative predictive values were 83% and 91%, respectively, and chance-corrected agreement (K) was 0.74 (CI 0.62-0.87). There was good agreement between the headache diagnoses obtained from the short interviews by nurses and the extensive interviews by neurologists. Short interviews based on recognition of typical headache descriptions seem to be an alternative and efficient way to identify migraine and tension-type headache sufferers among adolescents. The method can be useful in epidemiological research, e.g. in estimation of headache prevalence.
Co-Morbidity of Migraine and Major Depression in the Turkish Population
Authors: Kececi H , Dener S , Analan E
Published: December 2004

The aim of the present study was to estimate the co-morbidity of migraine and major depression in the Turkish population. The households were selected randomly from all district areas. The study included 947 subjects aged ≥ 18 years. The diagnosis of migraine was made according to the criteria of the International Headache Society. The diagnosis of major depression was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Migraine was identified in 163 subjects. Major depression was identified in 155 subjects, and in 53 subjects with migraine. The lifetime prevalence of major depression was approximately three times higher in persons with migraine in this Turkish population.
Electrophysiological Studies in Migraine: A Comprehensive Review of Their Interest and Limitations
Authors: Ambrosini A , de Noordhout AM , Sándor PS , Schoenen J
Published: December 2004

Electrophysiological methods may help to unravel some of the pathophysiological mechanisms of migraine. Lack of habituation is the principal and most reproducible interictal abnormality in sensory processing in migraineurs. It is found in evoked potential (EP) studies for every stimulation modality including nociceptive stimuli, and it is likely to be responsible for the increased intensity dependence of EP. We have hypothesized that deficient EP habituation in migraine could be due to a reduced preactivation level of sensory cortices because of hypofunctioning subcortico-cortical aminergic pathways. This is not in keeping with simple hyperexcitability of the cortex, which has been suggested by some, but not all, studies of transcranial magnetic stimulation (TMS). A recent study of the effects of repetitive TMS on visual EP strongly supports the hypothesis that migraine is characterized by interictal cortical hypoexcitability.

With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during migraine attacks.