bluuebunny/crossref_metadata_2025 huggingface dataset:
Limited Joint Mobility, Dupuytren's Contracture and Retinopathy in Type 1 Diabetes: Association with Cigarette Smoking
Authors: Eadington D. W. , Patrick A. W. , Collier A. , Frier B. M.
Published: July 2009

To examine the associations between cigarette smoking, connective tissue changes, and diabetic retinopathy, a detailed smoking history was elicited from 150 normotensive non‐diabetic subjects, and from 266 randomly selected adult patients with Type 1 diabetes, after examination for limited joint mobility, Dupuytren's contracture, and diabetic retinopathy. Mean insulin dose and current glycosylated haemoglobin concentrations were comparable in diabetic smokers and non‐smokers. The historical duration of smoking correlated with the duration of diabetes (r = 0.72, p < 0.001). In diabetic patients limited joint mobility was positively associated with retinopathy, being found in 73/147 (50%) patients with retinopathy compared with 20/114 (18%) without retinopathy (χ2 = 28.9, p < 0.001), and also with Dupuytren's contracture, 19/34 (56%) of patients with limited joint mobility having Dupuytren's contracture, compared with 76/232 (33%) of patients without Dupuytren's contracture (χ2 = 7.05, p < 0.01). Limited joint mobility was observed in 50% of diabetic smokers compared with 25% of non‐smokers (odds ratio = 2.87 (corrected for diabetes duration), 95% confidence interval 1.64–5.01). Diabetic retinopathy was weakly associated with smoking (odds ratio 1.09; 95% confidence interval 0.60–1.96). There was however an increased prevalence of background retinopathy among male smokers (50% vs 29%; χ2 = 6.88, p < 0.01). In non‐diabetic males limited joint mobility was observed in 37% of smokers but only in 11% of non‐smokers (NS), while 33% of smokers and 8% of non‐smokers had Dupuytren's contracture (p = 0.012). These results suggest that cigarette smoking contributes to the development of extra‐articular connective tissue changes in both diabetic patients and non‐diabetic subjects, and possibly to the development of diabetic retinopathy.
Vasopressin Secretion During Insulin‐induced Hypoglycaemia: Exaggerated Response in People with Type 1 Diabetes
Authors: Thompson C. J. , Thow J. , Jones I. R. , Baylis P. H.
Published: July 2009

Insulin hypoglycaemia causes a rise in plasma vasopressin concentrations in man and the rat, and vasopressin stimulates glucagon secretion and increases hepatic glucose output in man. Vasopressin has also been suggested to have an important synergistic role with corticotrophin releasing factor in the release of adrenocorticotrophin hormone, and a counter‐regulatory role for the hormone has been proposed. As diminished anterior pituitary hormone responses to hypoglycaemia have been reported in diabetes mellitus, we studied the plasma vasopressin responses to insulin‐induced hypoglycaemia in 10 patients with established Type 1 diabetes and 10 matched control subjects. Blood glucose fell from 4.5 ± 0.3 to 1.6 ± 0.1 mmol l‐1 (p < 0.001) in the diabetic group and from 4.6 ± 0.2 to 1.5 ± 0.2 mmol l‐1 (p < 0.001) in control subjects, with delayed blood glucose recovery in the diabetic patients. Plasma vasopressin rose in the diabetic patients from 0.9 ± 0.2 to 6.9 ± 2.8 pmol l‐1 (p < 0.001), a significantly greater rise (p < 0.05) than in the control subjects, 0.8 ± 0.1 to 2.4 ± 1.0 pmol l‐1 (p < 0.001). Plasma osmolalities remained unchanged and haemodynamic changes were similar in both groups. There is an exaggerated rise in plasma vasopressin concentrations in diabetic patients in response to insulin‐induced hypoglycaemia. The putative mechanisms and potential significance of the exaggerated rise are discussed.
The Cost of Diabetes
Authors: Gerard K. , Donaldson C. , Maynard A. K.
Published: July 2009

This paper estimates the cost of diabetes in England and Wales in 1984 to be in excess of £259.5 million. The costing methodology used follows the ‘cost of illness’ framework. This framework defines three elements for costing: direct, indirect and psychological, although the latter element is left out of the calculation because monetary valuations for this element have never been adequately estimated. Direct costs include resources used to prevent, detect, and treat diabetes. Indirect costs relate to the loss of productive output caused by absenteeism, early retirement, and premature mortality. The estimate which has been obtained is likely to be an underestimate because of the weaknesses and gaps in the data sets. The estimate of the total lost earnings from diabetes varied greatly according to the choice of absentee rate. If there was no significant difference between absenteeism in the diabetic community and the non‐diabetic community then the cost of diabetes would be £259.5 million. If on the other hand the diabetic community was prone to three times as much absenteeism as the non‐diabetic community then the cost of diabetes would rise to £602.5 million. The costs of diabetes as a subsidiary diagnosis are extremely difficult to identify. They have been estimated in this study to be £86 million but this is thought to be an overestimate. Nevertheless the cost of diabetes is significant and thus the search for more efficient treatment regimens may reduce such costs as well as enhance the quality of life of the patients concerned. Important policy conclusions to be drawn from this analysis are to improve the epidemiological underpinning upon which such estimates are based and to increase the use of economic evaluation, rather than ‘cost of illness’ methodology, to assist in priority‐setting in health care.
Testing Pupillary Autonomic Function with a Retinal Camera
Authors: Smith S. A.
Published: July 2009

A method for testing pupillary autonomic function with the Canon CR3–45NM retinal camera is described. Results agreed well with those obtained using the Polaroid CU5 close‐up camera in 20 non‐diabetic subjects and 29 diabetic patients (intrapair correlation coefficient = 0.97).
Smoking and Diabetes
Authors: Mühlhauser Ingrid
Published: July 2009

The frequency of smoking in diabetic patients is not appreciably different from that in the general population. As in non‐diabetic subjects, smoking is a major cardiovascular risk factor in diabetic patients. For young diabetic patients, smoking has been identified as a risk for macroproteinuric nephropathy. In respect of retinopathy, study results are more controversial. Recent studies also suggest smoking as a risk indicator for extra‐articular connective tissue changes and neuropathy. Patients who already present with vascular complications, pregnant women, and women who use oral contraceptive drugs appear to run a particularly high risk by smoking. Stopping smoking reduces the risk of vascular morbidity and mortality in non‐diabetic subjects. Although no comparable studies are available for diabetic populations, it should be assumed that the beneficial effects of stopping smoking are applicable to diabetic patients as well. Programmes to encourage diabetic patients to stop smoking are scarce and have not been successful.
Sickness Absence Among Insulin‐treated Diabetic Employees
Authors: Waclawskis E.R.
Published: July 2009

The aim of the present study was to investigate the sickness absence of insulin‐treated diabetic employees. A case‐control study using company sickness absence records for 1986 was performed on 59 diabetic patients and 59 control subjects matched by age, sex, and occupation. The patients had a similar frequency of absence to the control subjects (2.0 (range 0–7) and 1.7 (0–7) episodes yr−1, respectively). However, diabetic employees lost a larger number of working days (13.3 (0–101) vs 5.7 (0–52) days yr−1, p < 0.03), and had a greater average length of episode of absence (5.6 (0–55) vs 2.5 (0–28) days, p < 0.02). Males, manual workers, and those under 40 years of age accounted for significantly greater absence, but absence was also greater for diabetic employees than for control subjects in the other groups. Ten or more days were lost by 21 diabetic employees, but only 10 control subjects in 1986 (p < 0.05).
Antithyroid and Other Organ‐specific Antibodies in Saudi Arab Diabetic and Normal Children
Authors: Abdullah M.A. , Bahakim H. , Rab M.O. Gad Al , Halim K. , Salman H. , Abanamy A.
Published: July 2009

Sera from 162 Saudi Arab children were examined for autoantibodies to thyroid microsomes, thyroglobulin pancreatic islet cells, gastric parietal cells, and adrenocortical cells. The subjects included a control group (n = 76) and 86 children below 14 years with Type 1 diabetes. Antithyroid antibodies were detected in 8.1% of the diabetic group and in none of the control group. Parietal cell antibodies were found in 9.3% of the diabetic group and 4.4% of the control group; 14.6% of diabetic children and 2.2% of control children were positive for islet antibodies. However, 56.3% (9/16) of those who were tested at onset of diabetes had positive islet antibodies. In none of the children could we detect adrenocortical cell antibodies.
Prolonged Aldose Reductase Inhibition in Chronic Peripheral Diabetic Neuropathy: Effects on Microangiopathy
Authors: Jennings P.E. , Nightingale S. , Guen C. Le , Lawson N. , Williamson J.R. , Hoffman P. , Barnett A.H.
Published: July 2009

A 2‐year randomized placebo‐controlled double‐blind trial of 250 mg day−1 of the aldose reductase inhibitor Sorbinil in severe symptomatic chronic peripheral neuropathy was performed in 21 diabetic patients. Due to adverse reactions 8 patients completed the trial on Sorbinil and 6 patients on placebo. Despite differences in baseline neurophysiological parameters, duration of diabetes, and presence of retinopathy between the placebo and treatment groups, there were no initial differences in in vitro platelet aggregation, albumin excretion rate (AER) or muscle capillary basement membrane thickness. After 2 years the median deterioration in AER in the placebo group was 18.4 μg min−1 (range 2.6–64.8 μg min−1). This deterioration was significant (p < 0.03). The change in AER in the Sorbinil group was +1.25 (‐10.7 to +20.4) μg min−1, an insignificant change. In vitro platelet responsiveness to collagen and adenosine diphosphate (ADP) increased in the placebo group (median change max% collagen + 8 (+2 to +30)%; ADP +4.5 (0 to +20)% compared with a fall in the Sorbinil treated patients (median change; collagen −17.5 (‐2 to −40)%, p < 0.05; ADP, −4 (0 to −25)%, p < 0.05). Muscle capillary basement membrane thickness was measured in only 3 patients in each group and did not alter significantly during the trial. All 12 neurophysiological measurements showed no significant changes between the treatment and placebo groups. The data suggest that aldose reductase inhibition has effects on platelet reactivity and microalbuminuria.
Acute Changes in Plasma Non‐esterified Fatty Acid Concentration do not Change Hepatic Glucose Production in People with Type 2 Diabetes
Authors: Johnston P. , Hollenbeck C. , Sheu W. , Chen Y.‐D. I. , Reaven G. M.
Published: July 2009

The effect of changes in plasma non‐esterified fatty acid concentration (NEFA) on plasma glucose concentration, hepatic glucose production (Ra), and glucose disposal (Rd) rates was determined in 14 patients with Type 2 diabetes. Seven patients had relatively mild fasting hyperglycaemia (< 10.0 mmol l−1), whereas the remaining seven had relatively severe fasting hyperglycaemia (> 14.0 mmol l−1). Each patient was infused from 2000 to 0800 h with 3‐3H‐glucose on two occasions, with or without neutral fat emulsion and heparin (mild hyperglycaemia group), or with or without nicotinic acid (severe hyperglycaemia group). Plasma NEFA concentration increased from 0.33 ± 0.06 (± SE) to 4.78 ± 0.42 mmol l−1 in response to the lipid and heparin infusion, but plasma glucose concentration (7.8 ± 0.7 vs 7.4 ± 0.8 mmol l−1), Ra (0.44 ± 0.02 vs 0.46 ± 0.02 mmol m−2 min−1), and Rd (0.42 ± 0.02 vs 0.46 ± 0.02 mmol m−2 min−1) were unchanged. Nicotinic acid decreased plasma NEFA concentration from 0.54 ± 0.15 to 0.23 ± 0.08 mmol l−1, but plasma glucose (15.0 ± 1.0 vs 15.5 ± 1.4 mmol l−1), Ra (0.74 ± 0.07 vs 0.68 ± 0.07 mmol m−2 min−1), and Rd (0.73 ± 0.07 vs 0.68 ± 0.07 mmol m−2 min−1) were unchanged. The results indicate that acute changes in plasma NEFA concentration did not lead to any change in overnight glucose production or disposal rates.
The Skin Hyperaemic Response to Local Injection of Substance P and Capsaicin in Diabetes Mellitus
Authors: Boolell M. , Tooke J. E.
Published: July 2009

Recent studies have demonstrated impaired skin hyperaemia to local injury in diabetes mellitus. In order to gain insight into the mechanisms of impaired hyperaemia, dose‐response curves to intradermal substance P (25, 50, 100 pmol) and capsaicin (1.0, 2.5, 5.0 nmol) were examined before and after histamine blockade with chlorpheniramine, in 6 patients with uncomplicated Type 1 diabetes and 9 matched control subjects. Skin hyperaemia was measured indirectly as the peak laser Doppler flow in proximity to the area of hyperaemia. The response to the three doses of substance P was significantly lower in diabetic patients (0.37 ± 0.12 (± SD), 0.51 ± 0.12, 0.67 ± 0.09 V) than in control subjects (0.57 ± 0.15, 0.70 ± 0.19, 0.84 ± 0.21 V; p < 0.01). In contrast there was no significant difference in skin hyperaemia to capsaicin between diabetic patients (0.41 ± 0.07, 0.50 ± 0.09, 0.59 ± 0.09 V) and control subjects (0.41 ± 0.06, 0.52 ± 0.08, 0.63 ± 0.07 V). Following chlorpheniramine, the response to capsaicin remained unaltered (0.39 ± 0.07, 0.51 ± 0.05, 0.60 ± 0.07 in diabetic patients and 0.43 ± 0.08, 0.50 ± 0.10, 0.63 ± 0.07 V in control subjects), but there was a significant reduction in hyperaemia to substance P in both patients (20.4 ± 12.3% reduction, p < 0.05) and control subjects (20.6 ± 14.1% reduction, p < 0.05). It is suggested that impaired skin hyperaemia may represent decreased vascular reactivity to locally released substance P from peripheral nerve fibres.
Islet Function and Insulin Sensitivity in the Non‐diabetic Offspring of Conjugal Type 2 Diabetic Patients
Authors: Johnston C. , Ward W.K. , Beard J.C. , McKnight B. , Porte D.
Published: July 2009

To determine whether the genetic predisposition towards Type 2 diabetes was associated with a defect in either islet‐cell function or insulin action, 12 non‐diabetic offspring each of whose parents both had Type 2 diabetes were studied, together with 12 control subjects matched for age, sex, and weight. Fasting plasma glucose was higher in the offspring (5.5 ± 0.1 mmol I−1 (mean ± SE)) than in the matched controls (5.1 ± 0.1 mmol I−1) (p < 0.05). Using an IVGTT insulin sensitivity was not significantly lower in the offspring compared with their controls (3.1 ± 0.5 vs 3.8 ± 1.0 min−1 ***mU−1 I 10−4). There was no significant difference in any of the measures of insulin secretion (first‐ and second‐phase response to IV glucose, slope of glucose potentiation, and maximal glucose regulated insulin secretory capacity). Glucagon secretion measured before and after a stimulus of IV arginine at varying plasma glucose concentrations was virtually identical in the offspring and their controls. Among a total of 28 non‐diabetic subjects of differing body‐weights there was a significant inverse relationship between insulin sensitivity and insulin secretion. When adjusted for their generally lower insulin sensitivity, maximal insulin secretory capacity was reduced in the offspring (p = 0.038, one‐tailed t‐test). The results suggest that the genetic predisposition to Type 2 diabetes is not associated in young adults with any major pre‐morbid impairment in insulin secretion or insulin action but the relationship between the two may be abnormal. Islet A‐cell function appears to be normal.
A Project in Diabetes Education for Children
Authors: Bloomfield S. , Calder J.E. , Chisholm V. , Kelnar C.J.H. , Steel J.M. , Farquhar J. W. , Elton R.
Published: July 2009

Forty‐eight families with children less than 13 years old attending a paediatric diabetic clinic volunteered for a 2‐year randomized crossover trial to determine whether an informal education programme (diabetic club) could improve diabetic control. Group A attended the diabetic club for 10 afternoons of informal education in the first year, while Group B continued at the routine clinic (5 visits per year). For the second year Group A returned to the clinic, Group B attended the club. Glycosylated haemoglobin (HbA1) remained stable while attending the club but rose significantly (p < 0.01) while attending the clinic in both groups (HbA1 at baseline, 1 year, and 2 years: Group A, 9.6 (SD 1.2), 9.6(1.4), 10.7(2.1)%; Group B 8.9(1.3), 10.4(1.4), 10.5(1.4)% (normal reference range 4.7‐7.9%)). Other indices of control were unchanged. Diabetic problem‐solving scores of parents improved (p<0.01) but their knowledge of diabetes did not correlate with their child's HbA1. Dietary intake showed a reduction in percentage of energy taken as fat (40% vs 37.7%, p < 0.05) during club attendance. The percentage of parents reporting helpful social contact between families increased during their club year (Group A 50 to 78%, Group B 32 to 57%, p < 0.001). Psychological measurements remained unchanged. An education programme for diabetic children may stabilize diabetic control in the short term but this effect is not sustained. The main benefit was the support provided by increased social contact with families of other diabetic children within the informal framework of the diabetic club.
Health Belief Scales Developed Specifically for People with Tablet‐treated Type 2 Diabetes
Authors: Lewis K.S. , Jennings A.M. , Ward J.D. , Bradley C.
Published: July 2009

The design and development of scales to measure diabetes‐specific health beliefs of patients treated with oral hypoglycaemic agents and diet are described. The scales, which were developed from the responses of 187 tablet‐treated patients, measure perceived Benefits of, and Barriers to Treatment, and perceived Severity of, and Vulnerability to Complications of diabetes and other disorders unrelated to diabetes. Cronbach's alpha indicated that each scale was internally reliable (alpha = 0.67 to 0.89) and construct validity was indicated by expected correlations between the scales and other variables including measures of blood glucose control, body weight, and psychological well‐being. Thus, patients who were overweight and/or had higher glycosylated haemoglobin (HbA1) levels perceived their treatment to be less ‘Cost‐effective’ (Benefits less Barriers), rated Complications as being more severe, and reported greater Vulnerability for themselves and the ‘average person’ with diabetes to these Complications (p < 0.05 to p < 0.01). Furthermore, respondents with higher Depression and Anxiety scores and lower Positive Well‐being and Treatment Satisfaction scores reported greater Vulnerability to Complications for themselves and the ‘average person’, and also felt that their treatment was less ‘Cost‐effective’ (p < 0.01 to p < 0.001). The measures are likely to be particularly useful in studies which assess the efficacy of interventions in modifying health beliefs with a view to achieving desired behaviours. They may also be useful as an instrument of audit if indicators about the suitability of possible interventions are sought.
Postprandial Hyperglycaemia Following a Morning Hypoglycaemia in Type 1 Diabetes Mellitus
Authors: Fowelin J. , Attvall S. , von Schenck H. , Smith U. , Lager I.
Published: July 2009

The occurrence of hyperglycaemia following a morning hypoglycaemic episode was studied in nine patients with Type 1 diabetes. Each patient was studied twice, once following induced hypoglycaemia and once in a control study when hypoglycaemia was prevented by glucose infusion. After the initial hypoglycaemic/control period the patients were maintained on their regular insulin regimens and were given standard meals. Hypoglycaemia induced postprandial hyperglycaemia (3.1 ± 0.8 mmol I−1 above control) which lasted for about 8 h. Maximal growth hormone levels were seen 40 min after glucose nadir (control 7.8 ± 3.2, hypoglycaemia 74.0 ± 12.3 mU I−1) and the magnitude of the hyperglycaemia was related to the growth hormone levels following the hypoglycaemia (r = 0.80, p < 0.01).
Myogenic Microvascular Responses are Impaired in Long‐duration Type 1 Diabetes
Authors: Walmsley D. , Wiles P.G.
Published: July 2009

Post‐ischaemic hyperaemia is a complex physiological response. Peak flow is predominantly an arteriolar myogenic response, whilst viscoelasticity of supplying arteries determines speed of vasodilatation. Impaired post‐ischaemic hyperaemia has been described in neuropathic diabetic feet and might predispose to ulceration. However, the relationships of myogenic response and vasodilatation to diabetic control and microvascular complications are unclear. These relationships were therefore investigated using laser Doppler flowmetry to measure the hyperaemic response on the dorsum of the foot after 10 min ischaemia. Twenty control subjects were compared with 55 long‐duration Type 1 diabetic patients in groups of uncomplicated, retinopathic and neuropathic patients. Peak flow (median (interquartile range)) was reduced from 1.40 (1.20–1.61) in control subjects to 1.15 (0.80–1.29), 1.08 (0.75–1.26), and 0.95 (0.62–1.29) arbitrary units in the diabetic groups respectively (p= 0.012–0.004). Time to half peak flow was shorter in neuropathic diabetic patients compared with all other groups: 9.5 (7–19), 14.5 (5–25), 12.5 (6–20), and 4 (3–6) s, respectively (p= 0.027–0.011). Neuropathic patients also had the steepest initial slope of vasodilatation. Thus, in long‐duration diabetic patients, the myogenic peak post‐ischaemic hyperaemic response is impaired, but this impairment is not specifically associated with microvascular complications and was not related to recent blood glucose control. The shortened time to half peak flow and rapid vasodilatation in neuropathic patients is likely to reflect increased rigidity of their arteries.
Computer Based Quality Assessment of Hospital Capillary Blood Glucose Monitoring
Authors: Phillipou G. , Farrant R.K. , Phillips P.J.
Published: July 2009

A quality control (QC) programme to continually monitor the reliability of hospital ward capillary blood glucose levels has been developed based on a memory blood glucose meter interfaced to a portable microcomputer. Over a 38‐week period some 12 500 ward QC tests were performed by approximately 200 accredited operators. Although the mean weekly coefficients of variation were all less than 15%, there was a marked variation between wards, with the frequency of testing of patients the major factor influencing reliability. However an external laboratory‐based QC programme suggested a high degree of proficiency which was not achieved by any ward on internal QC assessment.
Prevalence and Age of Onset of Type 1 Diabetes in Adult Asians in The Coventry Diabetes Study
Authors: Simmons D.
Published: July 2009

Although Asians are known to have an excess of Type 2 diabetes when compared with Europids, the relative prevalence of Type 1 diabetes in Asians remains controversial. The Coventry Diabetes Study enumerated all adult diabetic subjects in the electoral ward of Foleshill (population 10 304) by a house‐to‐house survey. Residents treated with insulin were classified as having either Type 1 or Type 2 diabetes on the basis of plasma C‐peptide concentration and their diabetic history. Insulin treatment was received by 22% of Europids and 12% of Asians with previously diagnosed diabetes. Diabetic history was available for all and C‐peptide for 69% of insulin‐treated subjects. The age adjusted prevalence of Type 1 diabetes was 0.16 (95% CI 0.6–3.3)% in Europids and 0.12 (95% CI 0.4–2.7)% in Asians. Asians were found to have a significantly higher age at diagnosis (26 (range 19–34) vs 18 (6–29) years, p < 0.05) than Europids, and all were born outside of the United Kingdom. No Type 1 diabetes was diagnosed under 19 years of age in Asians while 5 of the 8 Europid subjects with Type 1 diabetes were diagnosed under this age. Type 1 diabetes does occur in Asians born outside the UK but either commences later in life or, if of earlier onset, precludes migration to the UK.
Placebo‐controlled Trial of the Effects of Guar Gum and Metformin on Fasting Blood Glucose and Serum Lipids in Obese, Type 2 Diabetic Patients
Authors: Lalor B.C. , Bhatnagar D. , Winocour P.H. , Ishola M. , Arrol S. , Brading M. , Durrington P.N.
Published: July 2009

Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo, guar gum (5 g three times daily) and metformin (500 mg three times daily) in a randomized double‐blind, double‐placebo, cross‐over study. Both active agents decreased fasting blood glucose from 11.4 ± 3.7 mmol l−1 (mean ± SD) to 8.6 ± 2.8 mmol l−1 on metformin (p<0.001) and to 9.5 ± 3.9 mmol l−1 on guar gum (p<0.01). Metformin significantly reduced the very low density lipoprotein (VLDL) cholesterol concentration from 0.62 (+ 0.73, − 0.34) mmol l−1 (geometric mean (+ SD, ‐ SD)) to 0.43 (+ 0.58, − 0.25) mmol l−1, (p<0.02), but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels. In patients with serum cholesterol > 6.5 mmol l−1 decreases in serum triglycerides from 3.29 (+ 3.27, − 1.64) to 2.46 (+ 2.55, − 1.25) mmol l−1 (p<0.02) occurred with metformin. In these patients guar gum produced a reduction in serum cholesterol (from 7.70 ± 0.90 to 6.41 ± 1.11 mmol l−1, p<0.01) due to an effect on low density lipoproteins. These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes.
Blood Glucose Control Determines the Renal Haemodynamic Response to Angiotensin Converting Enzyme Inhibition in Type 1 Diabetes
Authors: Jenkins D.A.S. , Cowan P. , Collier A. , Watson M.L. , Clarke B.F.
Published: July 2009

Elevation of glomerular filtration rate (GFR) is a feature of diabetes mellitus in humans and in animal models. Angiotensin II has been implicated as a mediator of GFR in diabetes. The acute effect of inhibition of angiotensin converting enzyme with captopril on renal haemodynamic and endocrine parameters was therefore studied in 14 normotensive male Type 1 diabetic patients, and the responses compared with those in five normal male control subjects. Following captopril 12.5 mg orally the diabetic patients exhibited an acute fall in GFR from 122 ± 3.8 to 113 ± 4.5 ml min−1 1.73‐m−2 (p < 0.02) and a rise in renal plasma flow (RPF) from 670 ± 57 to 797 ± 46 ml min−1 1.73‐m−2 (p < 0.01) which resulted in a fall in filtration fraction. This did not occur in normal control subjects. Natriuresis occurred only in normal control subjects. There was no change in urinary excretion of PGE2 or kallikrein in either group but excretion of 6‐keto‐PGF1α fell in the diabetic patients. There was a significant correlation between glycosylated haemoglobin and baseline RPF (rs = −0.79, p < 0.001) and filtration fraction (rs = 0.83, p < 0.001) that persisted when the change in these variables following captopril was analysed. Our results are compatible with the response to ACE inhibition in diabetic patients being secondary to inhibition of angiotensin II and suggest that this response may be related to blood glucose control.
Thyroid Hormone Replacement and Growth of Children with Subclinical Hypothyroidism and Diabetes
Authors: Chase H.P. , Garg S.K. , Cockerham R.S. , Wilcox W.D. , Walravens P.A.
Published: July 2009

Growth potential among people with Type 1 diabetes and subclinical hypothyroidism may be significantly reduced. Growth was evaluated in 25 children with diabetes who had thyromegaly and elevated thyrotrophin (TSH) levels. All patients appeared clinically euthyroid except for four with short stature. Basal growth rate was significantly lower (p < 0.005) in Group 1 (TSH < 50 mU I−1) and Group 2 (TSH level 10.1–50 mU I−1) than in patients with TSH levels between 5 and 10 mU I−1 (Group 3) or control diabetic children. Serum thyroxine (T4) levels were significantly lower (p < 0.05) in Group 1 than in Groups 2 or 3. Significant improvement in growth velocity after thyroxine treatment was observed in Group 1 patients compared with those in Groups 2 or 3 (p < 0.05). More prepubertal test children demonstrated improved growth after beginning thyroxine compared with matched diabetic controls (p < 0.02). Postpubertal subjects treated with thyroxine did not show significant differences in growth velocity compared with controls. Z‐scores for height were not different (p < 0.05; ANOVA) between control and test patients for any of the groups. Early detection of subclinical hypothyroidism by thyromegaly, reduced growth velocity, and elevated TSH levels, with institution of thyroxine treatment, can improve growth in prepubertal diabetic children.
Microproteinuria in Type 2 Diabetes Mellitus from Diagnosis
Authors: Martin P. , Hampton K.K. , Walton C. , Tindall H. , Davies J.A.
Published: July 2009

Glomerular and tubular microproteinuria precede the development of overt nephropathy in Type 1 diabetes mellitus. However, in Type 2 diabetes urinary protein excretion and its relationship to diabetic nephropathy has not been clearly characterized. Twenty consecutive, newly diagnosed patients with Type 2 diabetes, whose urine was Albustix‐negative and sterile on culture, were studied. Two timed overnight urine samples were collected at diagnosis, and after 2 months and 2 years, and excretion rates of albumin, α‐1‐microglobulin and N‐acetyl‐ß‐D‐glucosaminidase were calculated. HbA1c fell from 12.1 ± 2.4 % at diagnosis to 9.5 ± 1.5 % at 2 months and 9.6 ± 2.2 % at 2 years. Albumin excretion rate fell marginally from 6.5 (2.1–242.5) μg min−1 at diagnosis to 5.5 (1.7–274.0) μg min−1 at 2 months (p < 0.05) rising again to 6.1 (1.9–201.7) μg min−1 at 2 years. α‐1‐Microglobulin excretion rate fell from 13.5 (3.6–59.9) μg min−1 at diagnosis to 8.4 (2.9–16.1) μg min−1 2 months and 8.8 (1.8–54.1) μg min−1 at 2 years (both p < 0.05). Albumin excretion rate was found to correlate significantly with creatinine clearance at diagnosis (rs=0.61, p < 0.005), though not subsequently. In contrast, excretion rates of α‐1‐microglobulin and N‐acetyl‐ß‐D‐glucosaminidase correlated with HbA1c (rs = 0.68 and 0.66, respectively, p < 0.005 at diagnosis and rs = 0.57 and 0.53, p < 0.05 subsequently in both cases). After 24 months of treatment, all but two of the eight patients with abnormal albumin excretion rate at diagnosis had values within the normal range. The results suggest that in patients with Type 2 diabetes, raised albumin excretion rate at diagnosis is not indicative of persistent proteinuria.
Studies of Experimental Hosiery in Diabetic Neuropathic Patients with High Foot Pressures
Authors: Veves A. , Masson E.A. , Fernandox D.J.S. , Boulton A.J.M.
Published: July 2009

High plantar pressures and painless trauma are associated with the development of foot ulcers in diabetic patients. Padded hosiery has been reported to reduce plantar pressures in patients at risk of ulceration. Using the optical pedobarograph we have studied 10 patients who regularly wore experimental padded hosiery for 6 months. The hosiery continued to provide substantial and significant reduction in peak forefoot pressures at 3 months (mean reduction 15.5 %, p < 0.01) and 6 months (17.6 %, p < 0.01), although the level of reduction was less than that seen at baseline (31.3 %, p < 0.05). In addition, commercially available hosiery designed as sportswear has been tested, and compared with experimental hosiery. Although these socks (with high or medium density padding) provided significant pressure reduction versus barefoot (mean 17.4 % and 10.4 %, p < 0.01), this was not as great as that seen with experimental hosiery (27 %, p < 0.05). Thus the use of socks designed to reduce pressure stress on diabetic neuropathic feet is effective, and continues to be so for a considerable period of time. Commercially available sports socks may also have a place in the management of the diabetic insensitive foot.
Decreased Insulin Sensitivity in Offspring Whose Parents Both Have Type 2 Diabetes
Authors: Ramachandran A. , Snehalatha C. , Mohan V. , Bhattacharyya P. K. , Viswanathan M.
Published: July 2009

Offspring of two Type 2 diabetic parents have a high prevalence of diabetes and impaired glucose tolerance. Studies in normoglycaemic offspring have shown abnormal insulin responses. Twenty‐four non‐obese offspring having normal oral glucose tolerance were investigated by the insulin tolerance test for abnormalities of insulin sensitivity. Plasma insulin responses were measured during an oral glucose tolerance test. Although the plasma glucose responses during the OGTT were similar to the control values, the corresponding insulin responses were higher. The mean area under the insulin curve was 121 ± 29 (± SD) mU I−1 h in the control subjects and 203 ± 73 mU I−1 h in the offspring (p < 0.001). The mean KITT value in the offspring was 4.3 ± 1.9 min−1 × 100 which was significantly lower (p < 0.01) than the value of 6.2 ± 2.0 min−1 × 100 in the control subjects. The results suggest that some offspring of two Type 2 diabetic parents have low insulin sensitivity and the presence of hyperinsulinism may be a compensatory phenomenon.
Intramuscular Versus Subcutaneous Injection of Unmodified Insulin: Consequences for Blood Glucose Control in Patients with Type 1 Diabetes Mellitus
Authors: Vaag A. , Pedersen K. Damgaard , Lauritzen M. , Hildebrandt P. , Beck‐Nielsen H.
Published: July 2009

Using the perpendicular injection technique lean diabetic patients may often inject insulin intramuscularly (IM). Guided by ultrasound measurements of the subcutaneous (SC) thickness of the thigh, the aim of the present study was to re‐evaluate the absorption kinetics of unmodified insulin from IM and SC injection sites and to evaluate the consequences of IM injection of unmodified insulin for blood glucose control in Type 1 diabetic patients.T50%values (time until 50 % of the injected insulin is absorbed from the injection site) of SC injected, radioactively labelled, human unmodified insulin (125I‐Actrapid) were 338 ± 13 (± SE) min, 289 ± 27 min, and 287 ± 27 min during rest, light physical activity, and strenuous exercise, respectively. Intramuscularly injected unmodified insulin was absorbed faster,T50%232 ± 20 min, 113 ± 13 min, and 112 ± 5 min during the same levels of physical activity in the same order. When unmodified insulin (Actrapid) was given IM 30 min before breakfast, lunch, and dinner together with intermediate‐acting insulin (Protaphane) SC at 2200 h, a more physiological profile of plasma free insulin and a more stable blood glucose profile was obtained than with SC administration into the thigh. The coefficient of variation of blood glucose concentration during the study (3 days each route) was lower with IM than with SC injection of unmodified insulin (33 ± 4 vs 43 ± 3 %,p± 0.01). No difference in frequency of hypoglycaemic attacks was found and patients claimed that IM injection was no more painful than SC injection. These data suggest that IM injection of soluble insulin into the thigh is beneficial.
Glucose Metabolism in a Patient with Insulinoma Complicated by Hyperosmolar Non‐ketotic State
Authors: Ŝkrha J. , Páv J. , Svačina Ŝ. , Ŝrámková J. , Hilgertová J.
Published: July 2009

A case of a patient with organic hyperinsulinism complicated by the development of hyperosmolar state is described. The hyperosmolar state was induced by vomiting and dehydration during an acute urinary tract infection. Impairment of glucose metabolism was confirmed by the finding of reduced tissue sensitivity to insulin during a euglycaemic clamp.
An Assessment of the Accuracy of NovoPen 1 Delivery After Prolonged Use
Authors: Gordon D. , Wilson M. , Paterson K. R. , Semple C. G.
Published: July 2009

Forty‐five NovoPen 1 injection devices have been assessed for accuracy of insulin delivery. Twenty‐six pen‐injectors had been returned either because the device had developed structural faults or the patients had experienced unexpected deterioration in diabetic control. Twelve of these pen‐injectors were unusable. The remaining 14 pen‐injectors (‘faulty pen‐injectors’) were assessed by measuring the weight of insulin solution delivered in each of 10 depressions of the plunger and compared with similar measurements from 10 unused pen‐injectors (‘new pen‐injectors’) and 9 pen‐injectors (‘used pen‐injectors’) which had been used uneventfully for > 3 years. New pen‐injectors delivered insulin solution with an accuracy (median error) of 2.8 % and reproducibility (median SD) of 2.0 %. Used pen‐injectors had an accuracy of 2.3 % and reproducibility of 3.5 %. The 14 suspect pen‐injectors (‘faulty pen‐injectors’) demonstrated an accuracy of 2.8 % with reproducibility of 4.0 %. The reduction in reproducibility was due to faults in 4 pen‐injectors, 2 of which consistently delivered less insulin than expected, while a further two pen‐injectors were intermittently inaccurate.
Desensitization of the Platelet Aggregation Response to Adrenaline During Insulin‐induced Hypoglycaemia in Man
Authors: Trovati M. , Anfossi G. , Mularoni E. , Massucco P. , Cavalot F. , Mattiello L. , Emanuelli G.
Published: July 2009

The aim of the present study was to investigate the influence of insulin‐induced hypoglycaemia on platelet sensitivity to adrenaline and non‐adrenergic agonists in man. Twenty‐five healthy male subjects volunteered for the study. To evaluate the effects on platelets of different insulin‐adrenaline interrelationships, two experimental models were used. In the first, hypoglycaemia was induced by a 60‐min IV infusion of human insulin at the rate of 64 mU m−2min−1, whereas in the other the same insulin dose was administered as an IV bolus (3.84 U m−2). Throughout the studies, plasma glucose, insulin, and adrenaline were measured together with platelet sensitivity to adrenaline, ADP, platelet activating factor, collagen, and sodium arachidonate. In both studies, hypoglycaemia induced a reduction of platelet sensitivity to adrenaline (p= 0.006 in infusion andp= 0.045 in injection study). In particular, maximal aggregation to adrenaline fell from 47.9 ± 9.9 (± SE) to 31.1 ± 11.3% at the hypoglycaemic nadir in the infusion study, and from 64.6 ± 8.2 to 34.6 ± 10.3% at the hypoglycaemic nadir in the injection study. In the injection study an increase of platelet sensitivity to ADP (p= 0.05), platelet activating factor (p= 0.018), sodium arachidonate (p= 0.035), and collagen (p= 0.027) was also found, in agreement with observations already published using the infusion protocol. Thus, insulin‐induced hypoglycaemia increases platelet sensitivity to non‐adrenergic agonists and decreases platelet response to adrenaline.
Nephrotoxicity of Cyclosporin A in Patients with Newly Diagnosed Type 1 Diabetes Mellitus
Authors: Feldt‐Rasmussen B. , Jensen T. , Dieperink H. , Mandrup‐Poulsen T. , Nerup J. , Bendtzen K. , Andersen V. , Kemp E. , Leyssac P.P.
Published: July 2009

Renal function was studied in 18 patients with Type 1 diabetes mellitus. All were participating in the Canadian‐European randomized placebo‐controlled cyclosporin trial in newly diagnosed Type 1 diabetic patients, nine being randomized to placebo, and nine to cyclosporin A. During treatment for 12 to 18 months, cyclosporin A caused significant reductions in the glomerular filtration rate (before drug withdrawal, cyclosporin 97 ± 18 vs placebo 125 ± 16 ml min−1 1.73‐m−2, p < 0.05), renal plasma flow (454 ± 83 vs 536 ± 70 ml min−1 1.73‐m−2, p < 0.05), and lithium clearance (17 ± 3 vs 28 ± 5 ml min−1 1.73‐m−2, p < 0.05). The fractional proximal reabsorption was increased (0.82 ± 0.03 vs 0.78 ± 0.03, p < 0.05), and the fractional distal sodium reabsorption reduced (0.88 ± 0.03 vs 0.94 ± 0.02, p < 0.05). These results are in accordance with the hypothesis that the nephrotoxic effect of cyclosporin A results from a preferential constriction of afferent glomerular vessels. One year after withdrawal of the drug, all variables were similar in the two groups, except for blood glucose control which was worse in the cyclosporin A treated group. When corrected for differences in blood glucose control it appeared that in three out of nine patients glomerular filtration rate had not completely returned to the reference range of the placebo group. We conclude that the nephrotoxic side‐effects of cyclosporin A treatment for 1 year are reversible. There are, however, signs of minor and perhaps chronic renal injury.
High Plasma Insulin and Triglyceride Concentrations and Blood Pressure in Offspring of People with Impaired Glucose Tolerance
Authors: Zavaroni I. , Mazza S. , Luchetti L. , Buonanno G. , Bonati P.A. , Bergonzani M. , Passeri M. , Reaven G.M.
Published: July 2009

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non‐obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p<0.05, Student's t‐test) in offspring of parents with IGT (718±71 pmol I−1 h) than in the subjects whose parents had normal glucose tolerance (524±47 pmol I−1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17±0.11 vs 0.92±0.08 mmol I−1, 0.10 > p > 0.05), as were both systolic (132±5 vs 118±3 mmHg, p<0.05) and diastolic (79±3 vs 70±2 mmHg, p<0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.
The Variability of the Absorption of Subcutaneously Injected Insulin: Effect of Injection Technique and Relation with Brittleness
Authors: de Meijer P.H.E.M. , Lutterman J.A. , Van Lier H.J.J. , Laar A. van't
Published: July 2009

A comparison has been made of insulin absorption rate and its variability in healthy subjects (n= 12), matched Type 1 diabetic patients (n= 12), and brittle Type 1 diabetic patients (n= 13) after subcutaneous injection with a standardized injection technique. In each inividual 8 U of iodinated neutral human soluble insulin were injected twice, at the fat‐muscle boundary. Disappearance of radioactivity was measured for 8 h. Differences in absorption rate could not be demonstrated (T50207 ± 30 (± SD), 224 ± 73 and 217 ± 80 min in the three groups, respectively). Intra‐individual variance was similar in the three groups (intra‐individual SD of T5014 ± 9, 10 ± 6 and 12 ± 10%, respectively). Injection with the skinfold technique each patient usually employed, did not alter mean absorption rate or its variability significantly (T50179 ± 52 min; intra‐individual SD 12 ± 8%). In a group of Type 1 diabetic patients (n= 26) the absorption rate after deep injection was compared with that after superficial injection. No differences were found (T50207 ± 66 vs 236 ± 66 min). In some of these patients (n= 10) plasma free insulin and glucose concentrations were measured. The increase in free insulin concentrations was significantly different only at some time‐points, but insulin curves and plasma glucose concentrations did not differ significantly. Thus neither insulin absorption nor its variability differ between healthy subjects and diabetic patients, between deep and superficial subcutaneous injection, or between stable and brittle diabetic patients.
Comparison of Tolbutamide and Metformin in Elderly Diabetic Patients
Authors: Josephkutty S. , Potter J.M.
Published: July 2009

In a randomized double‐blind cross‐over study the efficacy, metabolic effects, and acceptability of metformin were compared with tolbutamide in 20 diabetic patients aged between 65 and 95 years. No significant differences were noted after treatment in blood glucose control (fasting plasma glucose, metformin 9.1 ± 2.8 mmol I−1, tolbutamide 8.3 ± 2.8 mmol I−1; mean change, metformin +1.1 mmol I−1, tolbutamide +0.02 mmol I−1, p = 0.215), domiciliary blood glucose control, fasting insulin, lactate, cholesterol or triglyceride levels. There was a significant difference in weight change between the two treatments (on metformin −2.0 kg, from 63.2 ± 11.8 to 61.2 ± 12.3; on tolbutamide, +1.6 kg, from 61.4 ± 11.1 to 63.0 ± 12.3; p = 0.001). Initial gastro‐intestinal side‐effects occurred in 30% of patients with metformin. These were transient and responded to temporary reduction in treatment dosage. Metformin could not be distinguished from tolbutamide in elderly diabetic patients, except in that it was associated with weight loss.
Haemostatic Measures in Type 2 Diabetic Patients with Microalbuminuria
Authors: Schmitz A. , Ingerslev J.
Published: July 2009

The major cause of disability and early mortality in Type 2 diabetes is cardiovascular disease. An enhanced urinary albumin excretion is strongly predictive of increased mortality, but the causal relationship behind this association is unclear. Abnormalities in the haemostatic system may be involved in the vascular pathology. We therefore studied the level of von Willebrand factor (vWf:Ag), factor VIII (VIII:Ag), fibrinogen, and fibronectin in male diabetic patients 50–70 years of age, with normal albumin excretion (n = 14), microalbuminuria (n = 14), and frank albuminuria (n = 7). Fourteen healthy age‐matched males served as a reference group. There were no significant differences between normo‐and micro‐albuminuric patients but vWf:Ag (p < 0.01), VIII:Ag (p < 0.01), and fibrinogen (p < 0.05) were increased in those with frank albuminuria. Urinary albumin excretion rate was significantly correlated to vWf:Ag (r = 0.46, p = 0.005), VIII:Ag (r = 0.45, p = 0.007), and fibrinogen (r = 0.49, p = 0.003). The known duration of diabetes was correlated to vWf and F VIII. The increased level of vWf:Ag in Type 2 diabetes and the significant association to the urinary albumin excretion rate may suggest a linkage between albuminuria and cardiovascular disease. However, the present study demonstrated no increase in haemostatic variables in patients with microalbuminuria as compared with those with normal albumin excretion.
Determining Diabetes Prevalence: a Rational Basis for the Use of Fasting Plasma Glucose Concentrations?
Authors: Finch C.F. , Zimmet P.Z. , Alberti K.G.M.M.
Published: July 2009

The World Health Organization and the National Diabetes Data Group each recommend a diagnostic cut‐off point for diabetes of 7.8 mmol l−1 for fasting plasma glucose concentrations as part of the diagnostic criteria for epidemiological studies. However, this cut‐off has been shown to be insensitive compared with a screening test based on 2‐h plasma glucose levels. In thirteen Pacific populations, from four ethnic groups (Asian Indian, Melanesian, Micronesian, and Polynesian), we have examined whether a different cut‐off point for fasting plasma glucose would be more accurate for obtaining an estimate of the prevalence of diabetes when compared with 2‐h levels. A fasting plasma glucose diagnostic cut‐off of 7.0 mmol l−1 gave an estimate of prevalence not significantly different from that based on the 2‐h plasma glucose in 12 of the 13 populations (mean difference 0.27, range −1.51 to +2.44,%). On the other hand, when a cut‐off of 7.8 mmol l−1 for fasting plasma glucose was used, the resulting prevalence over‐estimated the 2‐h glucose prevalence in all populations (mean difference 1.91, range 0.14–5.80,%). Thus for Pacific populations, a fasting plasma glucose cut‐off of 7.0 mmol l−1 provides estimates of prevalence that are equivalent to those based on 2‐h plasma glucose levels. In epidemiological studies designed to estimate diabetes prevalence, we recommend use of a fasting plasma glucose cut‐off of 7.0 mmol l−1 in preference to a detection level of 7.8 mmol l−1, if glucose loading is not possible. The low sensitivity associated with the 7.0 mmol l−1 cut‐off however, precludes its use as a definitive screening test for diabetes, particularly in the clinical setting.