Angiopoietic factors and retinopathy in pregnancies complicated with Type 1 diabetes.

AIMS: To evaluate the role of systemic angiopoietic factors in the progression of diabetic retinopathy during pregnancy. METHODS: In a prospective study of 26 pregnant women with diabetes and eight non-diabetic pregnant women, retinopathy was graded from fundus photographs. Plasma levels of angiopoietin-1, angiopoietin-2, human vascular endothelial growth factor A (hVEGF-A), and total soluble receptor of vascular endothelial growth factor (sVEGF) receptor-1 were measured during the first and third trimester and 3 months postpartum. RESULTS: In diabetic women, levels of angiopoietin-2 were 26.5 ng/ml (12.1-47.7) (median and range) during the first trimester, 2.9 ng/ml (0.6-3.5) during the third trimester, and 0.5 ng/ml (0.3-0.7) 3 months postpartum, compared with 44.3 (38.3-61.9), 5.7 (3.1-8.4) and 0.9 (0.6-4.9) ng/ml, respectively, in non-diabetic women (P = 0.002 between groups). Levels of angiopoietin-1 and sVEGF receptor-1 did not differ between the groups. Postpartum hVEGF-A levels were lowest in women with progression of retinopathy. In logistic regression analyses, progression of retinopathy during pregnancy was not explained by the levels of the angiopoietic factors. CONCLUSIONS: The circulating levels of angiopoietic factors in pregnant diabetic women were either lower than (Ang-2) or similar to (Ang-1, hVEGF-A, VEGFR-1) those levels observed in non-diabetic pregnant women. The levels of angiopoietic factors measured here appear not to be connected with the progression of retinopathy during pregnancy.     

Prevalence of retinopathy differs with age at onset of diabetes in a population of patients with Type 1 diabetes.

Aim The VISS study (Vascular complications in South‐east Sweden) investigates prevalence and incidence of vascular complications in a population with Type 1 diabetes, from a well‐defined geographical area and followed from diagnosis with HbA_1c measurement. Method The study population comprised all 440 patients with Type 1 diabetes onset before the age of 36 years, onset during 1983–1987, and at the time of onset living within the counties of Jönköping, Kalmar or Östergötland. Retinopathy was examined with fundus photography 1994–1995, and classified according to a modified Airlie House protocol. Results Fundus photographs from 390 patients were evaluated. In 277 (71%) patients no retinopathy was seen. The prevalence of retinopathy increased from 11% among patients < 5 years old at diabetes onset, to 48% among those 15–19 years old at diabetes onset, and then decreased to 30% for patients 30–35 years old at diabetes onset (P for χ² for linear trend for all ages 0.017, for age at onset 0–19 years P = 0.0003), without corresponding differences in duration or HbA_1c between patients with different onset age. Patients with HbA_1c in the highest quartile (> 8.3% HbA_1c) had a relative risk of 2.4 (95% confidence interval (CI) 1.7–3.2) of having any retinopathy compared with patients with lower HbA_1c, and a relative risk of 7.1 (95% CI 3.0–16.7) of having other forms of retinopathy than microaneurysms. Conclusion In patients with diabetes duration of 6–13 years, the prevalence of retinopathy is clearly related to glycaemic control. Furthermore, the risk of retinopathy varies with different age at onset, independently of differences in duration or glycaemic control. Diabet. Med. 19, 924–931 (2002)     

Development and progression of diabetic retinopathy in patients with Type 1 diabetes who are positive for GAD autoantibody.

AIMS: To investigate the relationship between autoantibodies to glutamic acid decarboxylase (GAD) and proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity in retinopathy. METHODS: Patients with Type 1 diabetes for more than 10 years who had been diagnosed under age 30 (13-28 years) were studied. They were classified into three groups. The PDR group consisted of 22 patients, the pre-PDR group was 26 patients, while the non-DR group was 32 patients who had Type 1 diabetes without retinopathy. Blood was collected to measure autoantibodies to GAD, and the relationship between PDR and GAD positivity was investigated in a cross-sectional study. RESULTS: The highest positivity rate of GAD autoantibodies was 50.0% in the non-DR group, followed by the pre-PDR group (30.8%) and the PDR group (18.2%). CONCLUSIONS: Production or existence of GAD autoantibodies may contribute to the prevention of retinopathy.     

Reduced microvascular hyperaemia in subjects at risk of developing Type 2 (non-insulin-dependent) diabetes mellitus

Summary Abnormalities of microvascular function may be important in the pathogenesis of diabetic microangiopathy. As such changes are already present at diagnosis in patients with Type 2 (non-insulin-dependent) diabetes mellitus, subjects at risk of developing the disease, who had elevated fasting plasma glucose concentrations below the diabetic range, were studied. The maximal microvascular hyperaemic response to local heating was determined in the feet of 11 subjects with fasting hyperglycaemia and 11 age- and sex-matched control subjects. There was reduced maximal hyperaemia in the subjects with fasting hyperglycaemia (1.01 [0.71–1.57]V, median and range), when compared to control subjects (1.41 [1.32–2.13]V, p <0.001). It is unlikely that this limited vasodilation is a result of the mild degree of hyperglycaemia observed in the subjects included in this study. Further studies are therefore required to address the possible mechanisms of limited microvascular reactivity in subjects at risk of developing Type 2 diabetes. [Diabetologia (1994) 37: 214–216] Received: 26 July 1993 and in revised form: 30 August 1993     

Impact of pregnancy on the progression of diabetic retinopathy in Type 1 diabetes.

AIMS: To evaluate the impact of pregnancy on the progression of diabetic retinopathy in women with Type 1 diabetes mellitus and to identify risk factors for the progression of retinopathy during pregnancy. METHODS: One hundred and seventy-nine pregnancies in 139 women with pregestational Type 1 diabetes were studied prospectively between January 1990 and December 1998. Dilated fundal examination was performed at booking, 24 weeks and 34 weeks or 4-6 weekly if retinopathy present at booking. Data were collected on glycaemic control (HbA(1c)) throughout pregnancy. RESULTS: Progression to proliferative retinopathy was seen in four (2.2%) pregnancies while moderate progression was seen in a further five (2.8%) pregnancies. Progression of retinopathy was significantly increased in women with duration of diabetes 10-19 years compared with duration < 10 years (10% vs. 0%; P = 0.007) and in women with moderate to severe background retinopathy at booking (30% vs. 3.7%; P = 0.01). Although HbA(1c) at booking was higher (7.5% vs. 6.6%; P = 0.08) and the fall in HbA(1c) between booking and 24 weeks was greater (1.6% vs. 1.2%; P = 0.2) in those women showing progression of retinopathy, these changes were not significant. CONCLUSIONS: Progression of retinopathy in pregnancy was uncommon (5.0% pregnancies) but was significantly more common in women with duration of diabetes > 10 years and in women with moderate to severe retinopathy at baseline. Laser therapy was needed in 2.2% pregnancies, which is much lower than that reported in earlier studies. Diabet. Med. 18, 573-577 (2001)     

Breastfeeding habits in families with Type 1 diabetes.

AIMS: Breastfeeding is acknowledged to be beneficial for child development. Women with diabetes may be more likely not to breastfeed their children because of neonatal morbidity and instability in diabetes control. The aim of this study was to assess the effect of maternal Type 1 diabetes on breastfeeding habits. METHODS: Full breastfeeding and any breastfeeding were reported in the first year of life in 1560 children born in Germany between 1989 and 2004. Of those, 997 children had a mother with Type 1 diabetes, and the remaining 563 children had a father or sibling with Type 1 diabetes. RESULTS: Fewer children of mothers with Type 1 diabetes were breastfed than children of non-diabetic mothers (77 vs. 86%; P < 0.0001) and, amongst breastfed children, there was a shorter duration of full breastfeeding (12 vs. 17 weeks; P < 0.0001) and any breastfeeding (20 vs. 26 weeks, P < 0.0001) in children of mothers with Type 1 diabetes compared with children of non-diabetic mothers. Other factors associated with reduced frequency and duration of breastfeeding were pre-term delivery (P < 0.0001), young maternal age (P < 0.0001), and firstborn children (P < 0.0001). After stratification for each of these factors, breastfeeding remained significantly less frequent and of less duration in children of mothers with Type 1 diabetes as compared with children of non-diabetic mothers. CONCLUSIONS: Mothers with Type 1 diabetes breastfeed their children less than international recommendations. Counselling to increase frequency and duration of breastfeeding may be warranted in this population.     

Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes.

AIMS: To study whether microalbuminuria, endothelial dysfunction and low-grade inflammation are associated with the presence and progression of diabetic retinopathy. METHODS: Patients with Type 2 diabetes (n = 328) attending a diabetes clinic were followed for 10 years and examined annually during the last 7 years. Retinopathy was assessed after pupillary dilatation by direct ophthalmoscopy (baseline) and two-field 60 degrees fundus photography (follow-up). Urinary albumin excretion, and markers of endothelial function (von Willebrand factor, tissue-type plasminogen activator, soluble E-selectin (sE-selectin), and soluble vascular cell adhesion molecule 1) and inflammatory activity (C-reactive protein and fibrinogen) were determined. RESULTS: The prevalence of retinopathy was 33.8%. The median diabetes duration at baseline was 7 years (interquartile range 2-12 years). The highest tertiles of baseline urinary albumin excretion and glycated haemoglobin (HbA(1c)) were associated with prevalent retinopathy: odds ratio (OR) 95% confidence interval (CI) 2.80 (1.44-5.46) and 2.19 (1.11-4.32), respectively. Progression of retinopathy occurred in 188 patients. The second and third tertiles of baseline sE-selectin were associated with progression of retinopathy [1.44 (1.04-2.01) and 1.61 (1.19-2.18)] but not independently of HbA(1c). None of the other markers was significantly associated with the presence or progression of retinopathy. High baseline HbA(1c) was significantly associated with progression of retinopathy: 1.65 (1.21-2.25). CONCLUSIONS: In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes the importance of glycaemic control in the development and progression of retinopathy.     

Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes.

AIMS: To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes. METHODS: A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA-2, insulin, thyroid globulin or thyroid peroxidase, or high-risk HLA-DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF-1alpha (MODY3) and neuroD1/beta2 (MODY6) genes were screened using the single-strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Within the cohort, we found one patient with a novel mutation, R321H (CGC-->CAC) in exon 5 of the HNF-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/beta2 gene, and two patients with autoantibodies to SOX13. CONCLUSIONS: Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.     

Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus.

AIMS: The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines. SUBJECTS AND METHODS: Forty-two non-diabetic first-degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA-2 antibody). Follow-up for 9-11 years confirmed high vs. moderate diabetes risk in islet autoantibody-positive vs. -negative relatives. Cytokines and chemokines were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of classic Th1-associated cytokines (IFN-gamma, IL-12, IL-18) or Th2/Treg-associated cytokines (IL-5, IL-10, IL-13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in the multiple islet autoantibody-positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P = 0.00005), but not in the autoantibody-negative group. CONCLUSION: Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up-regulation of CCL3 and CCL4 vs. down-regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.     

Plasma leptin concentration in patients with Type 2 diabetes: relationship to cardiovascular disease risk factors and insulin resistance.

AIMS: The aim of this study was to evaluate the relationship of obesity, leptin, insulin resistance and C-reactive protein (CRP) with coronary heart disease (CHD) risk factors in patients with Type 2 diabetes mellitus (DM) with CHD compared with those with Type 2 DM without CHD. METHODS: Leptin, CRP (high sensitivity assay), fasting plasma insulin, glucose, HbA(1c) and full lipid profile were determined in 58 Type 2 diabetic patients with CHD and 87 Type 2 DM patients without CHD. RESULTS: were compared between those with and without CHD. Univariate correlation as well as logistic regression analyses were used to relate these markers with traditional CHD risk factors. RESULTS: Leptin showed significant correlations with BMI (r = 0.59; P < or = 0.0001), waist circumference (r = 0.45; P < 0.0001), CRP (r = 0.36; P < 0.0001), and fasting insulin (r = 0.53; P < 0.0001) as well as with systolic (r = 0.23; P = 0.007) and diastolic (r = 0.23; P = 0.007) blood pressure. However, when those with and without CHD were compared only age (P < 0.0001), duration of diabetes (P < 0.001) and degree of microalbuminuria (P = 0.02) were significantly higher in patients with CHD. Leptin (P = 0.49), CRP (P = 0.19) and lipid parameters were not significantly different between the two groups. CONCLUSION: Our study confirms a relationship between leptin and CRP with CHD risk factors. The lack of significant difference when patients with and without CHD are compared may be due to the potential confounding effects of treatment with aspirin and statins.     

Risk factors for coronary disease and stroke in previously hospitalized African-Americans with Type 1 diabetes: a 6-year follow-up.

AIMS: To report the 6-year incidence of, and risk factors for, cardiovascular disease (CVD), either coronary disease or stroke, in previously hospitalized African-Americans with Type 1 diabetes mellitus. METHODS: African-Americans (n = 483) with Type 1 diabetes were re-examined as part of a 6-year follow-up. At both visits, patients underwent a structured clinical interview, which included history of either coronary disease or stroke, ocular examination and masked grading of seven stereoscopic fundus photographs, blood pressure measurements, and administration of the Beck Depression Inventory. Biological measurements included blood and urine assays. RESULTS: Of the 483 patients who had a 6-year follow-up, 449 had no evidence of CVD at the baseline examination. Of these 449 patients, 51 (11.4%) developed any CVD-42 (9.3%) coronary disease and 14 (3.1%) a stroke. Six-year incidence of any CVD was significantly associated with older age (P < 0.0001) and longer duration of diabetes (P < 0.0001) at baseline. Multiple logistic regression showed that baseline older age, higher body mass index, higher diastolic blood pressure, proteinuria, retinopathy severity and being depressed were significant and independent risk factors for incidence of any CVD. CONCLUSION: Six-year incidence of CVD is high in previously hospitalized African-Americans with Type 1 diabetes. Risk factors appear to include older age, higher body mass index, higher diastolic blood pressure, proteinuria, retinopathy severity and depression.     

Intercellular adhesion molecule-1 (ICAM-1) polymorphism is associated with diabetic retinopathy in Type 2 diabetes mellitus.

AIMS: Leucocyte adhesion to the diabetic retinal vasculature has been implicated in the pathogenesis of diabetic retinopathy. We evaluated the relationship between genetic polymorphisms in leucocyte and endothelial cell adhesion molecules and diabetic retinopathy in Type 2 diabetes mellitus. METHODS: We determined ICAM-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), and leucocyte endothelial adhesion molecule-1 (LECAM-1) genotypes in 81 patients with and 50 without diabetic retinopathy. RESULTS: The frequency of ICAM-1 469KK genotype and K allele were significantly higher in the patients with diabetic retinopathy than in those without retinopathy (genotype 42% vs. 20%, chi2 = 6.70, P = 0.035; allele 66% vs. 50%, chi2 = 6.49, P = 0.011). With regard to the PECAM-1 V125L and LECAM-1 P213S polymorphisms, there were no significant associations between the distribution of genotypes or allele frequencies and the presence of diabetic retinopathy. Independent of other risk factors, the ICAM-1 469KK genotype was associated with a 3.51-fold increased risk for retinopathy. CONCLUSIONS: These data suggest that the ICAM-1 469KK genotype could be a genetic risk factor for retinopathy in Type 2 diabetes mellitus.     

The contribution of nitric oxide and vasodilatory prostanoids to bradykinin-mediated vasodilation in Type 1 diabetes.

AIMS: To investigate the effect of bradykinin on endothelial tone in normoalbuminuric Type 1 diabetic patients and specifically whether any changes are mediated through nitric oxide or prostaglandins. METHODS: Forearm blood flow was measured using venous occlusion plethysmography at baseline and after brachial artery infusions of incremental doses of bradykinin (50, 100 and 200 ng/min) in 15 patients with Type 1 diabetes and 13 non-diabetic controls. Forearm blood flow at baseline and following bradykinin was then re-examined after local infusion of L-NMMA, a nitric oxide synthase inhibitor, and L-NMMA with indomethacin, a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (4.46 +/- 1.11 vs. 3.41 +/- 1.23 ml/min/100 ml, respectively; P = 0.07). After infusion of L-NMMA and L-NMMA with indomethacin, there was a similar reduction in blood flow responses to bradykinin in both groups. There was no significant difference between the diabetic patients and control subjects in the percentage reduction in forearm blood flow following L-NMMA (16.55 vs. 18.12%, respectively, P = 0.94) and L-NMMA with indomethacin (47.1 vs. 37.3%, respectively, P = 0.14). CONCLUSIONS: This study demonstrates that bradykinin-stimulated vasodilation is mediated by both nitric oxide and prostaglandin release from the endothelium in patients with Type 1 diabetes and normoalbuminuria, and in healthy control subjects. We have also shown that the relative contributions of nitric oxide and prostaglandin to bradykinin-mediated vasodilation are similar in these diabetic patients compared with non-diabetic subjects.     

Elevated long-term glycated haemoglobin precedes proliferative retinopathy and nephropathy in Type 1 (insulin-dependent) diabetic patients

Summary The importance of glycaemic control for the development of proliferative retinopathy and nephropathy was assessed by monitoring glycated haemoglobin for 5 years or more before the diagnosis of these complications. The study comprised Type 1 (insulin-dependent) diabetic patients diagnosed at an age less than 31 years, and with diabetes duration 25 years or less. They were followed for an average of 7.9 years with 3.3 measurements per year. Of 172 patients screened for retinopathy 60 had no retinopathy, 104 had background retinopathy, and 8 had proliferative retinopathy. The mean HbA_1c (95% confidence intervals) of the groups was 6.4% (6.2–6.7%), 7.3% (7.1–7.5%) and 8.9% (8.1–9.6%), respectively (p<0.0001); the mean duration of diabetes was 12, 18, and 17 years. Of 186 patients 7 had nephropathy (albuminuria>200 mg/l). Mean HbA_1c in patients without nephropathy was 7.0% (6.8–7.1%) and in patients with nephropathy 8.8% (7.8–9.9%,p<0.001). Mean diabetes duration was 16 years in both groups. Multiple logistic regression including mean HbA₁₀, age at onset, duration, sex, and hypertension, was for both proliferative retinopathy and nephropathy significant only for mean HbA_1c. In all cases, proliferative retinopathy and nephropathy were preceded by poor glycaemic control over several years, suggesting that these complications are caused by poor glycaemic control.     

Association of immune mediators at diagnosis of Type 1 diabetes with later clinical remission.

AIMS: We tested the hypothesis that systemic concentrations of cytokines, chemokines or soluble cytokine receptors predict or accompany clinical remission in Type 1 diabetes (T1D). METHODS: In a prospective, multicentre study, 48 patients with newly diagnosed T1D and 55 age-matched healthy control subjects were investigated. Blood was drawn 3-7 days after the diagnosis and then 3-4 months later. Patients were grouped into partial remitters or non-remitters by the degree of clinical improvement defined by HbA(1c) (threshold 7.5%) and daily insulin dose (threshold 0.38 IU/kg/day). Systemic concentrations of 17 immune mediators were analysed in serum or plasma. In addition, autoantibodies against insulin (IAA), IA-2 (IA-2A) and GAD65 (GADA) were quantified. RESULTS: All 17 immune mediators showed remarkable intra-individual stability in their systemic concentrations over time. As a consequence, partial remission was not accompanied by changes in mediator levels except for a moderate decrease of interleukin (IL)-1ra concentrations (P = 0.02) and IL-10 concentrations (P = 0.01) in non-remitters. Baseline levels were associated with the later clinical course in that low levels of interferon gamma (P = 0.01), IL-10 (P = 0.03) and IL-1R1 (P = 0.009) concentrations were observed in partial remitters. CONCLUSIONS: We conclude that the systemic immunoregulatory state at diagnosis of T1D is predictive of clinical improvement during the remission phase. There was no general change in systemic immune reactivity in the months after diagnosis and initiation of insulin therapy.     

Aerobic fitness and hand grip strength in Type 1 diabetes: relationship to glycaemic control and body composition.

AIM: To clarify the relationship of aerobic fitness and handgrip strength with glycaemic control (HbA1c), body composition and lipid profile in Type 1 diabetes. METHODS: Aerobic capacity (Chester Step Test), handgrip strength and body composition (bioelectrical impedance) were measured in 141 patients with Type 1 diabetes. RESULTS: Aerobic capacity correlated positively with HbA1c and lean body mass and negatively with body mass index and fat mass. Handgrip strength correlated positively with aerobic capacity and negatively with HbA1c and fat mass. In addition, there was a positive correlation between HbA1c and total cholesterol. CONCLUSION: Patients with Type 1 diabetes who have good aerobic capacity have poorer glycaemic control. However, this was an observational study and the results must be interpreted with caution. Further investigation into how these patients manage blood glucose during exercise is required.     

Association of intercellular adhesion molecule 1 polymorphisms with retinopathy in Chinese patients with Type 2 diabetes.

AIMS: To investigate the relationship of the K469E and G241R polymorphisms of the intercellular adhesion molecule 1 (ICAM-1) gene with diabetic retinopathy in Chinese patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: One hundred and seventy-two Chinese patients with Type 2 diabetes and 80 normal control subjects were recruited. Patients with diabetes were placed into two groups: the diabetic retinopathy (DR) group and the non-diabetic retinopathy (NDR) group. The DR group was subdivided into those with proliferative retinopathy (PDR) and non-proliferative retinopathy (NPDR). Genomic DNA was prepared using the hydroxybenzene-chloroform extraction method. Genotypes and alleles were detected by polymerase chain reaction-heteroduplex-single-strand conformation polymorphism (PCR-HA-SSCP) analysis combined with gene sequencing. RESULTS: The patients with retinopathy had an increased frequency of the K469K genotype compared with both the patients without retinopathy and the control subjects (61.4 vs. 40.0 and 35.0%, respectively; chi(2) = 8.280 and 13.952, respectively; P < 0.05). The frequency of the K allele in the DR group was higher than in the NDR group and control subjects (75.4 vs. 58.8 and 61.3%, respectively; chi(2) = 9.693 and 11.219, respectively; P < 0.05). Genotype and allele frequencies were similar in the NDR group and control subjects, and in the PDR and NPDR groups. CONCLUSION: The ICAM-1 gene K469E polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes. Patients with the K469K genotype were more likely to have diabetic retinopathy than patients with the K469E or E469E genotype.     

Reduced hyperaemia following skin trauma: evidence for an impaired microvascular response to injury in the diabetic foot

Summary The hyperaemic response to standard needle injury within dorsal foot skin was investigated in normal and Type 1 (insulin-dependent) diabetic subjects using laser Doppler flowmetry. The normal response was maximal within 15 min, localised, prolonged and biphasic. In 20 normal subjects and three groups of long-duration Type 1 diabetic patients (20 without complications; 20 with laser-treated retinopathy; 15 with neuropathy and retinopathy), the median (interquartile range) peak hyperaemic responses were 1.766 (1.220–1.970), 1.485 (1.342–1.672), 0.997 (0.705–1.203) and 1.030 (0.718–1.369) arbitrary units, respectively. Compared to normal and uncomplicated diabetic groups, peak flow was significantly reduced in the retinopathic (p<0.0001) and neuropathic (p=0.001 and 0.007, respectively) groups. There was no significant difference between the normal and uncomplicated diabetic groups, nor between the retinopathic and neuropathic groups. There was no association of the hyperaemic response with blood sugar, HbA_1c, or duration of diabetes. Diabetic patients who have microvascular complications, with or without neuropathy, have an associated impairment of microvascular response to mechanical injury which might predispose to infection and poor wound healing.     

Hypoglycaemia with insulin aspart: a double-blind, randomised, crossover trial in subjects with Type 1 diabetes.

AIMS: To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy. METHODS: In this multinational, double-blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA(1c) < 8.0%) were symmetrically randomised to two 16-week treatment periods on either type of insulin, both injected 0-5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4-week washout. RESULTS: The rate of major nocturnal (24.00-06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47-1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA(1c) remained constant, slightly below 7.7% on both treatments. CONCLUSIONS: The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.