Neale Cohen

Benefits for Type 2 Diabetes of Interrupting Prolonged Sitting With Brief Bouts of Light Walking or Simple Resistance Activities

OBJECTIVE To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 ± 6 years old) underwent the following 8-h conditions on three separate days (with 6–14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h−1) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions. RESULTS Compared with SIT, both activity-break conditions significantly attenuated iAUCs for glucose (SIT mean 24.2 mmol · h · L−1 [95% CI 20.4–28.0] vs. LW 14.8 [11.0–18.6] and SRA 14.7 [10.9–18.5]), insulin (SIT 3,293 pmol · h · L−1 [2,887–3,700] vs. LW 2,104 [1,696–2,511] and SRA 2,066 [1,660–2,473]), and C-peptide (SIT 15,641 pmol · h · L−1 [14,353–16,929] vs. LW 11,504 [10,209–12,799] and SRA 11,012 [9,723–12,301]) (all P < 0.001). The iAUC for triglycerides was significantly attenuated for SRA (P < 0.001) but not for LW (SIT 4.8 mmol · h · L−1 [3.6–6.0] vs. LW 4.0 [2.8–5.1] and SRA 2.9 [1.7–4.1]). CONCLUSIONS Interrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postprandial glucose, insulin, C-peptide, and triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical.

Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics.

AIM To investigate severe hypoglycaemia (SH) in adults with type 1 diabetes and its associations with impaired awareness of hypoglycaemia (IAH), clinical, psychological and socio-demographic factors. METHODS Attendees of three specialist diabetes clinics in Melbourne, Australia completed questions about frequency of SH in the past six months; impaired awareness of hypoglycaemia (Gold score); and measures of general emotional well-being (WHO-5), diabetes-specific positive well-being (subscale of W-BQ28), diabetes-related distress (PAID) and fear of hypoglycaemia (HFS). RESULTS Of 422 participants (mean ± SD age 37.5 ± 15.0 years; 54% women), 78 (18.5%) reported at least one SH event and 86 (20.5%) had IAH. SH and IAH frequencies were similar at all clinics. In total, 194 SH events were reported, with 10 people experiencing 40% of events. Compared with those without SH, participants with SH had longer diabetes duration, were younger at diabetes onset and more likely to have IAH (p<0.01). Those with SH had greater fear of hypoglycaemia and diabetes-related distress, poorer general emotional well-being, and lower diabetes-specific positive well-being, (p<0.01). There were no associations with age, gender, insulin regimen or HbA1c. CONCLUSIONS This study has identified that SH and IAH in Australian adults with type 1 diabetes exist at similar levels to those reported in US and European research. SH was significantly associated with IAH and fear of hypoglycaemia. Assessment of hypoglycaemia, IAH and psychological well-being as part of a routine diabetes clinic visit was well accepted by attendees and enabled identification of those who may benefit from medical, educational or therapeutic interventions.

Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes

Objective: Prolonged sitting is increasingly recognized as a ubiquitous cardiometabolic risk factor, possibly distinct from lack of physical exercise. We examined whether interrupting prolonged sitting with brief bouts of light-intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2 diabetes (T2D). Methods: In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men; mean ± SD; 62 ± 6 years) consumed standardized meals during 3 × 8 h conditions: uninterrupted sitting (SIT); sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity walking); and sitting + half-hourly bouts of simple resistance activities for 3 min (SRAs), each separated by 6–14 days washout. Resting seated BP was measured hourly (mean of three recordings, ≥20-min postactivity). Plasma noradrenaline was measured at 30-min intervals for the first hour after meals and hourly thereafter. Results: Compared with SIT, mean resting SBP and DBP were significantly reduced (P < 0.001) for both light-intensity walking (mean ± SEM; −14 ± 1/−8 ± 1 mmHg) and SRA (−16 ± 1/−10 ± 1 mmHg), with a more pronounced effect for SRA (P < 0.05 versus light-intensity walking). Similarly, mean plasma noradrenaline was significantly reduced for both light-intensity walking (−0.3 ± 0.1 nmol/l) and SRA (−0.6 ± 0.1 nmol/l) versus SIT, with SRA lower than light-intensity walking (P < 0.05). Mean resting heart rate was lowered by light-intensity walking (−3 ± 1 bpm; P < 0.05), but not SRA (−1 ± 1 bpm). Conclusion: Interrupting prolonged sitting with brief bouts of light-intensity walking or SRA reduces resting BP and plasma noradrenaline in adults with T2D, with SRA being more effective. Given the ubiquity of sedentary behaviors and poor adherence to structured exercise, this approach may have important implications for BP management in patients with T2D.

Diabetes: advances in treatment

The increasing prevalence of diabetes worldwide is cause for concern both in terms of associated morbidity and increasing health costs. This review aims to focus on new and emerging treatments for type 1 and type 2 diabetes. There has been recent focus on diabetes prevention both for type 1 and type 2 diabetes. Prevention programme including lifestyle measures and oral hypoglycaemic agents have shown up to 61% reduction in the development of type 2 diabetes in patients with impaired glucose tolerance or impaired fasting glucose. Little progress has been made to date on type 1 diabetes prevention although current work is focusing on T‐cell immunomodulation therapy and beta cell regeneration. Management of type 2 diabetes has been improved by the recent introduction of the peroxisome proliferator‐activated receptor‐gamma agonists and more recently by the incretins including glucagons like peptide analogues and dipeptidyl peptidase‐4 inhibitors. This article focuses on the benefits and restrictions of these new agents. The new insulin analogues glargine and detemir have made significant improvements in the management of type 1 diabetes both in terms of improvement in glycaemic control and in reducing hypoglycaemia rates. Inhaled insulin also shows promise for needle‐free treatment of diabetes and these insulins are currently undergoing phase 3 trials. Insulin infusion pumps are becoming more sophisticated and increasingly popular in the management of type 1 diabetes. Many studies have shown benefits for improved glycaemic control and reduced rates of hypoglycaemia with pump treatment compared with multiple daily injections. Pancreas and islet cell transplantation are the subject of ongoing research, but currently require immunosuppressive treatment regimes. The main limitation is lack of availability of donor pancreases. There is much hope that new treatments outlined in this review will result in improved outcomes in the treatment of diabetes.

Long-Term Metabolic Effects of Continuous Subcutaneous Insulin Infusion Therapy in Type 1 Diabetes

BACKGROUND Continuous subcutaneous insulin infusion (CSII) and intensive multiple daily insulin injections (iMDI) program are treatment options in patients with type 1 diabetes not achieving optimal glycemic control. The long-term effects of CSII in patients with type 1 diabetes in comparison with those educated for iMDI are poorly documented. RESEARCH DESIGN AND METHODS Medical records for patients commenced on CSII or undertaking an iMDI program between 2000 and 2011 were extracted. Change in hemoglobin A1c (HbA1c), hypoglycemia, and weight were analyzed. Prior to CSII or iMDI commencement, all patients were on basal bolus analog insulin. Data from blood glucose meter downloads before and 6 months after CSII and iMDI were also analyzed. RESULTS One hundred twenty-six CSII and 121 iMDI patients were studied, with mean (±SD) follow-up of 39±26 and 48±26 months, respectively. For CSII, HbA1c was significantly lower than baseline at every time period up to 36 months. Peak HbA1c reduction was 0.64% at 6 months, following which the HbA1c change declined. For iMDI, HbA1c was significantly reduced only at 6 months, by 0.15%. Glucose meter data were available for 119 patients. CSII-treated patients had a significant decrease in mean glucose and glucose SD with no change hypoglycemia at 6 months compared with baseline; no differences were observed for iMDI-treated patients. CONCLUSIONS CSII in type 1 diabetes is associated with improved glycemic control with no increase in hypoglycemia. HbA1c improvement declined over time, suggesting a need for re-education after CSII commencement. The iMDI program did not have significant glycemic benefits.

An exploratory trial of basal and prandial insulin initiation and titration for type 2 diabetes in primary care with adjunct retrospective continuous glucose monitoring: INITIATION study

AIMS To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support. METHODS Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation. RESULTS Ninety-two patients mean age (range) 59 (28-77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002). CONCLUSIONS Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077.

Improvement in albuminuria in patients with type 2 diabetes after laparoscopic adjustable gastric banding.

Purpose: To determine the effects of laparoscopic adjustable gastric banding (LAGB) on albuminuria in patients with obesity, type 2 diabetes mellitus (T2DM) and established diabetic nephropathy. Methods: A retrospective analysis of clinical records from a tertiary diabetes service identified obese patients with T2DM who had micro- or macroalbuminuria prior to LAGB surgery. Clinical data from follow-up appointments including albuminuria were analysed. Results: A total of 23 T2DM patients were included in the final study. Of 7 patients with macroalbuminuria at baseline, 2 reverted to normoalbuminuria, 2 reverted to microalbuminuria and 3 remained with macroalbuminuria on their final recording in the 36-month period of follow-up. Of 16 patients with microalbuminuria, 9 reverted to normoalbuminuria, while 6 remained with microalbuminuria. Conclusion: This study demonstrates significant improvements in albuminuria in patients with established diabetic nephropathy following LAGB. These results suggest the potential for LAGB to improve or reverse renal damage in patients with T2DM.

The emerging role of metformin in gestational diabetes mellitus.

Metformin use during pregnancy is controversial and there is disparity in the acceptance of metformin treatment in women with gestational diabetes mellitus (GDM) in Australia. Despite short term maternal and neonatal safety measures, the placental transfer of metformin during GDM treatment and the absence of long‐term safety data in offspring has regulators and prescribers cautious about its use. To determine the current role in GDM management, this literature review describes the physiological changes that occur in GDM and other forms of diabetes in pregnancy (DIP) and international changes in guidelines for GDM diagnosis. Management options are considered, with a focus on the evolving evidence for metformin, its mechanism of action, the maternal, foetal and neonatal outcomes associated with its use and benefit vs risk when compared with the current gold standard, insulin. Investigation reveals a favourable balance of evidence to support the safety and long‐term benefits, to mother and child, of using metformin as an alternate to insulin for treatment of GDM. Recent findings of the gastrointestinal‐directed action of metformin are at least as important as the hepatic effect and the availability of a novel delayed‐release metformin dose form to exploit this new information provides a product and therapeutic strategy ideally suited to the use of metformin in GDM.

Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape)

To test the hypothesis that a ‘basal plus’ regimenadding once‐daily main‐meal fast‐acting insulin to basal insulin once dailywould be non‐inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction.

Potential of small molecule protein tyrosine kinase inhibitors as immunomodulators and inhibitors of the development of diabetes

Type 1 (previously insulin dependent or juvenile onset) diabetes is an auto-immune disease for which there is no current prevention or cure. The anti-cancer agent and protein tyrosine kinase inhibitor imatinib is used successfully in the treatment of chronic myeloid leukaemia. Imatinib has shown a variety of immunomodulatory effects in animals and humans and it has recently been reported to inhibit the development of hyperglycaemia in two unrelated mouse models of diabetes and in one human case study. Although the biochemical target has not been characterised, potentially this represents a major advance for the treatment and prevention of diabetes.