Helen Lunt

Elevated glycine betaine excretion in diabetes mellitus patients is associated with proximal tubular dysfunction and hyperglycemia.

In an ambulatory population of diabetic subjects (Type 1 and Type 2), the urine excretion of the renal osmolyte, glycine betaine, was compared to known markers of glycemic control, renal dysfunction and to the excretion of related betaines, including trigonelline, proline betaine, carnitine and acetyl-carnitine. Of the 85 subjects, 20 patients had urine glycine betaine concentrations above the reference range for normal subjects. Plasma glycine betaine concentrations were within reference ranges for normal subjects. Patients with elevated glycine betaine excretion tended to have lower plasma glycine betaine concentrations, but this did not reach statistical significance. One way analysis of variance found excretion is independent of treatment, duration of diagnosed diabetes, blood pressure and body mass index (BMI). An association between glycine betaine excretion and glycemic control was observed with statistically significant correlations occurring with both plasma glucose (r = 0.43, P < 0.001) and glycated haemoglobin (HbA1c) (r = 0.35, P < 0.005). The excretion of carnitine, acetyl-carnitine and proline betaine were related to glycine betaine excretion (r = 0.49, P < 0.001; r = 0.40, P < 0.001; r = 0.27, P < 0.05, respectively). Urine carnitine and acetyl-carnitine concentrations were also related to plasma glucose concentrations (r = 0.30, P < 0.01). Increased urine retinol binding protein concentrations (RBP), a marker of proximal tubular dysfunction, correlated with elevated urine glycine betaine excretion and plasma HbA1c (r = 0.28, P < 0.01). These results suggest poor glycemic control is associated with the increase in urine glycine betaine, carnitine, acetyl-carnitine and RBP excretion in diabetic patients. However, < 50% of the observed increase in glycine betaine excretion has been accounted for by the variables measured, suggesting other unidentified processes may also be involved.

High intensity interval training in a real world setting: a randomized controlled feasibility study in overweight inactive adults, measuring change in maximal oxygen uptake.

Background In research clinic settings, overweight adults undertaking HIIT (high intensity interval training) improve their fitness as effectively as those undertaking conventional walking programs but can do so within a shorter time spent exercising. We undertook a randomized controlled feasibility (pilot) study aimed at extending HIIT into a real world setting by recruiting overweight/obese, inactive adults into a group based activity program, held in a community park. Methods Participants were allocated into one of three groups. The two interventions, aerobic interval training and maximal volitional interval training, were compared with an active control group undertaking walking based exercise. Supervised group sessions (36 per intervention) were held outdoors. Cardiorespiratory fitness was measured using VO2max (maximal oxygen uptake, results expressed in ml/min/kg), before and after the 12 week interventions. Results On ITT (intention to treat) analyses, baseline (N = 49) and exit (N = 39) O2 was 25.3±4.5 and 25.3±3.9, respectively. Participant allocation and baseline/exit VO2max by group was as follows: Aerobic interval training N =  16, 24.2±4.8/25.6±4.8; maximal volitional interval training N = 16, 25.0±2.8/25.2±3.4; walking N = 17, 26.5±5.3/25.2±3.6. The post intervention change in VO2max was +1.01 in the aerobic interval training, −0.06 in the maximal volitional interval training and −1.03 in the walking subgroups. The aerobic interval training subgroup increased VO2max compared to walking (p = 0.03). The actual (observed, rather than prescribed) time spent exercising (minutes per week, ITT analysis) was 74 for aerobic interval training, 45 for maximal volitional interval training and 116 for walking (p =  0.001). On descriptive analysis, the walking subgroup had the fewest adverse events. Conclusions In contrast to earlier studies, the improvement in cardiorespiratory fitness in a cohort of overweight/obese participants undertaking aerobic interval training in a real world setting was modest. The most likely reason for this finding relates to reduced adherence to the exercise program, when moving beyond the research clinic setting. Trial Registration ACTR.org.au ACTRN12610000295044

A population-based study of bone mineral density in women with longstanding type 1 (insulin dependent) diabetes

This study aimed to explore multiple determinants of BMD (bone mineral density) in 99 women with long-standing type 1 diabetes, recruited from a population based register of insulin users. BMD was measured using DEXA (dual energy X-ray absorptiometry) at the femoral neck and lumbar spine, age adjusted Z scores were calculated and results compared to those of healthy volunteers. The median age of diabetic subjects was 42 years and the median duration of diabetes was 27 years. BMD was positively associated with body mass index and height at both the lumbar spine and femoral neck. There was a positive association with oral contraceptive pill use and lumbar spine BMD, and peripheral vascular disease was negatively associated with femoral neck BMD. No correlation was seen with either age or duration of diabetes and absolute BMD values. Mean Z score at the femoral neck was -0.12 (95% confidence interval -0.37 to +0.12). At the lumbar spine, the corresponding value was -0.21 (-0.44 to +0.02). Pre- and post-menopausal values for the diabetic subjects and healthy volunteers were found to be similar. In summary, axial BMD values in subjects with long-standing diabetes were similar to those observed in healthy non diabetic populations.

Measurement of breath acetone concentrations by selected ion flow tube mass spectrometry in type 2 diabetes.

Selected ion flow tube-mass spectrometry (SIFT-MS) can measure volatile compounds in breath on-line in real time and has the potential to provide accurate breath tests for a number of inflammatory, infectious and metabolic diseases, including diabetes. Breath concentrations of acetone in type 2 diabetic subjects undertaking a long-term dietary modification programme were studied. Acetone concentrations in the breath of 38 subjects with type 2 diabetes were determined by SIFT-MS. Anthropomorphic measurements, dietary intake and medication use were recorded. Blood was analysed for beta hydroxybutyrate (a ketone body), HbA1c (glycated haemoglobin) and glucose using point-of-care capillary (fingerprick) testing. All subjects were able to undertake breath manoeuvres suitable for analysis. Breath acetone varied between 160 and 862 ppb (median 337 ppb) and was significantly higher in men (median 480 ppb versus 296 ppb, p = 0.01). In this cross-sectional study, no association was observed between breath acetone and either dietary macronutrients or point-of-care capillary blood tests. Breath analysis by SIFT-MS offers a rapid, reproducible and easily performed measurement of acetone concentration in ambulatory patients with type 2 diabetes. The high inter-individual variability in breath acetone concentration may limit its usefulness in cross-sectional studies. Breath acetone may nevertheless be useful for monitoring metabolic changes in longitudinal metabolic studies, in a variety of clinical and research settings.

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period

Background Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. Methods Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). Results Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality = 0.52) and urine (index of individuality = 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and −35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to −80% in plasma). Conclusions Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value.

Self-reported changes in capillary glucose and insulin requirements during the menstrual cycle.

Perimenstrual changes in glycaemic control and insulin requirements have been reported in Type 1 diabetes. A population‐based sample of 124 women with Type 1 diabetes, aged 18 to 40 years, were questioned regarding perimenstrual changes in their self‐monitored capillary blood glucose and insulin regimen. Sixty‐one percent of women noted perimenstrual changes in capillary blood glucose. The commonest pattern was a premenstrual rise in glucose. Thirty‐six percent of all study participants were making adjustments to their insulin dose in response to these changes in capillary blood glucose. There was no statistical difference in the mean glycated haemoglobin of subjects making perimenstrual adjustments in insulin (79.1 mmol mol−1 haem) compared to subjects who noted cyclical capillary glucose changes but did not adjust insulin (73.0 mmol mol−1 haem). Sixty‐seven percent of subjects taking the fixed dose oestrogen/progesterone oral contraceptive pill (OCP) noted perimenstrual changes in glucose. In summary, a third of the women surveyed made perimenstrual adjustments to their insulin dose, but there was no evidence to suggest that this behaviour was associated with improved glycaemic control. Use of the fixed dose combined oral contraceptive pill did not eliminate perimenstrual changes in glucose.

Women and Diabetes

There is an increasing demand by women with diabetes for information on health issues such as pre‐conception planning, contraceptive choices, hormone replacement therapy, and osteoporosis prevention. The risks and benefits of therapeutic approaches in these areas will be influenced by the presence of diabetes. Other health issues discussed in this article, which are unique to women with diabetes, include the effect of the menstrual cycle on glycaemic control and insulin requirements, and insulin omission in order to lose weight.

Diabetes in New Zealand.

While the ethnic make up of the New Zealand population is predominantly European, the Polynesian population, consisting of indigenous New Zealand Maori and more recent immigrants from the other Pacific Islands is increasing rapidly. The prevalence of diabetes in these Polynesians is high. There is also an increasing prevalence of obesity, and obesity is a greater problem amongst Polynesian people. The number of elderly people in the population is increasing. All of these demographic changes are increasing the incidence and prevalence of Type 2 diabetes. The incidence of Type 1 diabetes is also rising, although the reasons for this are unknown. Diabetic nephropathy is the most common cause of end stage renal failure in New Zealand. Polynesian people with diabetes, and in particular Maori, have a very high rate of diabetic nephropathy and develop renal failure at a more rapid rate than European patients with nephropathy relating to Type 1 diabetes. The propensity for Maori patients with Type 2 diabetes to develop renal failure may relate to a younger age at the onset of diabetes, a genetic susceptibility to nephropathy, and socio-economic or cultural factors leading to less adequate medical care.

Metformin increases plasma ghrelin in Type 2 diabetes.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Metformin, unlike the other major antihyperglycaemic drugs, is not associated with weight gain. * Ghrelin is an appetite-stimulating hormone whose concentrations vary in relation to food, obesity and diabetes control. * Reports are conflicting about how metformin affects ghrelin concentrations, and this study was aimed at resolving this issue in patients with Type 2 diabetes. WHAT THIS STUDY ADDS * In this study an increase in ghrelin concentrations was seen in response to metformin treatment in patients with Type 2 diabetes. * This effect was opposite to what might be expected if the effect of metformin on weight control was mediated via suppression of ghrelin. * It is likely that the ghrelin response was secondary to improved glycaemic control. * Meal time changes in appetite and satiety did not correlate with changes in ghrelin, which suggests ghrelin may not be important in meal initiation. AIMS Metformin treatment of Type 2 diabetes is not usually associated with weight gain, and may assist with weight reduction. Plasma ghrelin concentrations are inversely associated with obesity and food intake. Metformin might therefore affect ghrelin concentrations, although previous studies have shown variable results in this regard. The primary aim of this study was to determine the effect of metformin on plasma ghrelin, appetite and satiety in patients with Type 2 diabetes. METHODS Eighteen patients with Type 2 diabetes were studied before and after 6 weeks of metformin treatment, which was titrated to 1 g b.d. On the study days patients were fed standard meals of 390 kcal at 08.00 and 12.30 h, plasma samples were collected at 15- and 30-min intervals, and appetite and satiety were measured on visual analogue scales. Changes in the area under the concentration-time curves (AUCs) of plasma ghrelin, insulin, glucose, appetite and satiety were assessed and examined for correlations with metformin AUCs. Changes in fasting adiponectin and leptin were also measured. RESULTS Treatment with metformin increased the mean AUC (07.30-16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001). No changes were detected in hunger and satiety, or in fasting adiponectin or leptin concentrations. There were no clear correlations between metformin plasma concentrations (AUC) and changes in plasma glucose, insulin or ghrelin. CONCLUSIONS Treatment of Type 2 diabetes with metformin was associated with increased plasma ghrelin concentrations, without associated changes in hunger and satiety.

Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.

To evaluate the efficacy and safety of basal insulin peglispro (BIL) with those of insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (T2D).