Lynda Molyneaux

TBI or not TBI: that is the question. Is it better to measure toe pressure than ankle pressure in diabetic patients?

Aims Measurement of ankle blood pressure is a simple method of assessing lower limb arterial blood supply. However, its use in diabetes has been questioned due to the presence of medial artery calcification. Measurement of toe blood pressure has been advocated as an alternative but it is technically more difficult. The aim of this study was to obtain information to guide clinicians as to when pressure measurements should be taken at the toe.

Long-Term Complications and Mortality in Young-Onset Diabetes: Type 2 diabetes is more hazardous and lethal than type 1 diabetes

OBJECTIVE To evaluate long-term clinical outcomes and survival in young-onset type 2 diabetes (T2DM) compared with type 1 diabetes (T1DM) with a similar age of onset. RESEARCH DESIGN AND METHODS Records from the Royal Prince Alfred Hospital Diabetes Clinical Database, established in 1986, were matched with the Australian National Death Index to establish mortality outcomes for all subjects until June 2011. Clinical and mortality outcomes in 354 patients with T2DM, age of onset between 15 and 30 years (T2DM15–30), were compared with T1DM in several ways but primarily with 470 patients with T1DM with a similar age of onset (T1DM15–30) to minimize the confounding effect of age on outcome. RESULTS For a median observation period of 21.4 (interquartile range 14–30.7) and 23.4 (15.7–32.4) years for the T2DM and T1DM cohorts, respectively, 71 of 824 patients (8.6%) died. A significant mortality excess was noted in T2DM15–30 (11 vs. 6.8%, P = 0.03), with an increased hazard for death (hazard ratio 2.0 [95% CI 1.2–3.2], P = 0.003). Death for T2DM15–30 occurred after a significantly shorter disease duration (26.9 [18.1–36.0] vs. 36.5 [24.4–45.4] years, P = 0.01) and at a relatively young age. There were more cardiovascular deaths in T2DM15–30 (50 vs. 30%, P < 0.05). Despite equivalent glycemic control and shorter disease duration, the prevalence of albuminuria and less favorable cardiovascular risk factors were greater in the T2DM15–30 cohort, even soon after diabetes onset. Neuropathy scores and macrovascular complications were also increased in T2DM15–30 (P < 0.0001). CONCLUSIONS Young-onset T2DM is the more lethal phenotype of diabetes and is associated with a greater mortality, more diabetes complications, and unfavorable cardiovascular disease risk factors when compared with T1DM.

Augmentation of central arterial pressure in Type 2 diabetes

Aims  Aortic systolic blood pressure has been shown to be augmented in Type 1 diabetes, indicative of more rapid pulse wave reflection due to increased arterial stiffness. This abnormality is more pronounced in diabetic males. The aim of this study was to examine the effects of diabetes on augmentation of aortic systolic pressure in subjects with Type 2 diabetes.

Why Does Ethnicity Affect Prevalence of Gestational Diabetes? The Underwater Volcano Theory

To study why gestational diabetes (GDM) is more common in some ethnic groups than others, we tested the hypothesis that GDM is more common in people who are temporally closer to developing non‐insulin‐dependent (Type 2) diabetes mellitus (NIDDM). The prevalence of GDM and the mean age of affected women in each major ethnic group were determined. From our database of NIDDM 6052 patients, the mean age of onset in each ethnic group was calculated and the mean difference between age of developing GDM and age of developing NIDDM derived (NIDDM–GDM age gap). This age gap was used to adjust for the susceptibility to GDM of each group. The overall prevalence of GDM was 6.7 % (CI 6.0 %–7.4 %). In Anglo‐Celtic women it was 3.0 % (CI 2.3 %–3.7 %). For the other ethnic groups the prevalence and odds ratio (OR) were: Chinese (15.0 % CI 11.8 %–18.2 % OR 5.6), Vietnamese (9.6 % CI 6.6 %–12.5 % OR 3.6), Indian (16.7 % CI 9.8 %–23.5 % OR 6.4), Arabic (7.3 % CI 4.6 %–10.1 % OR 2.5) and Aborigines (10.1 % CI 3.8 %–16.4 % OR 3.7). The OR for susceptibility to GDM did not change after adjustment for BMI and maternal age and it correlated significantly with the NIDDM–GDM age gap (r = −0.85; p = 0.03). However, it fell substantially after adjustment for NIDDM‐GDM age gap. For women of different ethnic origins there is a difference in the time gap between their pregnancies and the time at which they would on average be expected to develop diabetes. This difference may be an important factor underlying the higher prevalence of GDM in some ethnic populations.

Timing Is Everything: Age of Onset Influences Long-Term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors

OBJECTIVE—To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia. RESEARCH DESIGN AND METHODS—Retinopathy data from 624 patients with a type 2 diabetes duration of 20–30 years (group A) were analyzed by stratifying patients according to age of onset of diabetes and glycemic control. Retinopathy status was scored clinically as per a modified Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate possible bias due to a higher attrition from comorbidities in those with later-onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter duration (10–12 years, group B) were similarly studied. RESULTS—Prevalence and severity of retinopathy was significantly higher in the younger-onset, group A patients. When further stratified according to mean A1C, retinopathy risk remained increased in younger-onset patients. The greatest impact was seen in those with a mean A1C >9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for age of diagnosis <45, 45–55, and >55 years, respectively, P = 0.003). By logistic regression, earlier type 2 diabetes onset is associated with increased retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9, 1.1, and 1 for age of onset <45, 45–55, and >55 years, respectively). Similar results were found in group B patients. CONCLUSIONS— These data suggest an increased inherent susceptibility to diabetic retinopathy with earlier-onset type 2 diabetes. This further supports the importance of delaying development of diabetes and also implies a need for more stringent metabolic targets for younger individuals.

Insensate versus painful diabetic neuropathy: the effects of height, gender, ethnicity and glycaemic control

AIMS/HYPOTHESIS To study similarities and differences between people with insensate or painful diabetic peripheral neuropathy, particularly in relation to height, gender, ethnicity and glycaemic control. METHODS We studied prospectively 2610 patients with Type 2 diabetes attending our Diabetes Centre. Subjects were compared according to degree of sensory loss, and presence or absence of neuropathic pain. The effects of gender and ethnicity were evaluated by studying patients in different height bands. RESULTS Insensate neuropathy and painful neuropathy was present in 11.4 and 3.3% of subjects, respectively. Age, duration of diabetes, height, vibration perception and HbA(1c) (P<0.0001) were independent determinants of insensate neuropathy, whereas only duration of diabetes and vibration perception (P<0.0001) were predictive of pain. There was more insensate neuropathy in males (OR 1.9) and anglo-celtics (OR 1.4) but stratification by height showed that these effects were due to height. Height has no influence on the development of pain. CONCLUSIONS There is significant overlap but also considerable dichotomy in the two major forms of diabetic sensory peripheral neuropathy. The insensate type is more explainable by duration, degree of hyperglycaemia and length of peripheral nerves, factors that are likely to reflect severity of underlying structural nerve damage. Glycaemic control was not a predictor of painful neuropathy.

The metabolic syndrome in type 1 diabetes: does it exist and does it matter?

The significance of the metabolic syndrome in type 1 diabetes is not well understood. This study aimed to estimate its prevalence and attendant complications. Four hundred twenty-seven type 1 diabetic subjects were grouped according to the presence or absence of metabolic syndrome (WHO criteria). Macro- and microvascular complications were compared between the groups as individual and as composite endpoints. Data were analyzed for the total cohort and in subgroups according to duration of diabetes quartiles (<6.9, 7-12.9, 13-19.9, and >20 years) and year of presentation. Fifteen percent of individuals fulfilled the WHO criteria for metabolic syndrome, and of these, 26.9% were insulin resistant, as compared with 3.4% of those without metabolic syndrome [odds ratio (OR)=8.9, P=.001]. Both BMI and metabolic syndrome showed an increasing trend from 1992 to 2003. Those with metabolic syndrome required significantly higher insulin dosage [0.9 (0.7-1.2) vs. 0.6 (0.5-0.9) units/kg, P=.03], were older [35.0 (26.2-47.3) vs. 29.7 (23.4-36.4) years, P=.002], and had longer duration of diabetes [19.7 (10.7-25.6) vs. 12.1 (6.3-17.9) years, P=.0001]. They also had a significantly higher macrovascular composite endpoint (OR=3.3, P=.02) as well as higher macrovascular and microvascular composite endpoint (OR=3.1, P=.0001). The prevalence of stroke (OR=22.8, P=.008), peripheral vascular disease (OR=7.3, P=.05), and severe retinopathy (OR=3.7, P=.01) is higher in subjects with metabolic syndrome in the >or=20-year quartile group; in addition, these subjects have higher macrovascular composite endpoint (OR=3.9, P=.03) and macrovascular and microvascular composite endpoint (OR=2.9, P=.03). This remained so even when subjects with albuminuria were excluded. Some individuals with type 1 diabetes can also have metabolic syndrome. They are more prone to complications and require even more intensive glycemic control and reduction of macrovascular risk factors.

Administration of ascorbic acid and an aldose reductase inhibitor (Tolrestat) in diabetes : Effect on urinary albumin excretion

The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA1c, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon’s signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.

The effects of dexfenfluramine on blood glucose control in patients with type 2 diabetes

Dexfenfluramine has been shown to promote weight loss in overweight people. The present double‐blind study was designed to test whether the addition of dexfenfluramine to conventional oral hypoglycaemic treatment would promote weight loss and improve blood glucose control in overweight patients with Type 2 diabetes. The 34 patients studied were randomly assigned to dexfenfluramine or placebo therapy which was added for 12 weeks to their existing treatment regimens of metformin with or without a sulphonylurea. Dexfenfluramine treatment was associated with a significant reduction in weight (98.7 ± 5.0 (± SE) vs 94.9 ± 5.2 kg; p <0.001), BMI (35.0 ± 1.2 vs 33.6 ± 1.9 kg m−2; p < 0.001), HbA1c (7.5 ± 0.3 vs 6.3 ± 0.2%; p < 0.001), fructosamine (313.9 ± 17.6 vs 274.3 ± 10.4 μmol I−1; p < 0.01), systolic (137 ± 5 vs 128 ± 6 mmHg; p < 0.05), and diastolic blood pressure (85 ± 2 vs 73 ± 3 mmHg; p < 0.001). At the end of the study period, the dexfenfluramine treated group had a significantly lower HbA1c (6.3 ± 0.2 vs 7.2 ± 0.4; p <0.05), fructosamine level (274.3 ± 10.4 vs 313.3 ± 16.1 μmol I−1; p < 0.05) and diastolic blood pressure (73 ± 3 vs 81 ± 3 mmHg; p < 0.03) when compared with the placebo group. In those patients treated with dexfenfluramine, the reduction in HbA1c and blood pressure did not correlate with the decrease in BMI (r = 0.44 and 0.12, respectively). Dexfenfluramine is a valuable adjunct to the treatment of the overweight patient with Type 2 diabetes.

Which diabetic patients should receive podiatry care? An objective analysis

Abstract