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Diabetes, Insulin Resistance and Obesity

Team: Jim Mann, Lisa Te Morenga, Alex Chisholm, Rachel Taylor, Kirsten Coppell, Rachel McLean, Kim Meredith, Chris Baldy, Victoria Farmer, Ashley Duncan, Michelle Harper

Edgar Diabetes and Obesity Research

Diabetes

Diabetes and its complications are important health problems throughout the world. The incidence of type 2 diabetes is increasing in New Zealand and other countries. In New Zealand, total diagnosed and undiagnosed adult prevalence rate was recently estimated to be nearly 7%. In Maori the prevalence was estimated at 9-10% and in Pacific men and women it was estimated to be 14% and 16% respectively (Key Findings of the 2008/2009 Adult Nutrition Survey, Ministry of Health 2011).

Optimal Diets for the Prevention of Diabetes

A diet high in carbohydrate and fibre is currently recommended for the general population (and for those with diabetes or at high risk of developing diabetes). However many people, especially Maori, find this diet unacceptable and prefer high protein or high fat dietary regimes, which are promoted as more beneficial for weight loss. These diets have had little formal evaluation except in small studies of short duration. None has assessed the effect on risk indicators after weight loss has plateaued. The original study by our group to explore this compared diets higher in fat or protein than is currently recommended with the conventional diet, in insulin resistant individuals, to determine whether the approaches differ in their potential to promote weight loss and improve risk factors for type 2 diabetes and cardiovascular disease during and after the initial weight loss phase. The results of this study have now been published in major international journals and have received major coverage in the media (More information).

The metabolic syndrome describes a cluster of risk factors for type 2 diabetes (T2DM). Nutritional approaches which favourably influence these factors might be expected to reduce the risk of T2DM. Two further dietary intervention studies have been undertaken to examine the effects of macronutrient composition on clinical and metabolic determinants associated with the metabolic syndrome.

Previous research suggests that moderately high-protein diets may be more appropriate than conventional low-fat, high-carbohydrate diets for individuals at high risk of T2DM. However in most such studies sources of dietary carbohydrate were not specified or may not have been appropriate. Thus in the first study two weight-loss diets – one moderately high in protein and the other high in fibre-rich, minimally-processed cereals and legumes – were compared to determine whether a relatively high-protein diet has the potential to confer greater benefit. Participants lost weight on both diets, reduced body fat and showed improvement in other markers of metabolic risk. However participants on the high protein diet had more favourable improvements (Download publication).

Dietary approaches to reducing risk of T2DM typically emphasise fat and energy restriction, but for many achieving and maintaining weight loss is difficult. Diets that focus on substantially altering macronutrient distribution rather than energy restriction are promising alternatives. The second study examined the effects on body composition, insulin sensitivity and other metabolic risk factors, of dietary advice including moderate increases in protein and fibre, without specifying energy intake compared with standard dietary recommendations. Women following the diet high in protein and fibre lost significantly more weight and fat than participants following the standard dietary advice. Total and LDL cholesterol were also significantly lower after the HPHFib diet (See abstract).

LOADD Study
Until recently 'lifestyle therapy' (appropriate diet and exercise) was the cornerstone of treatment for type 2 diabetes (T2DM). Drugs to lower high blood glucose, reduce raised blood pressure, and to treat abnormal blood lipid levels are more widely prescribed than previously, and the importance of lifestyle may have been overlooked. This research examined the extent to which an intensive dietary intervention can further improve glucose, blood pressure and lipids levels, over and above the effects of recommended drugs. Patients with established T2DM on appropriate diabetes and cardiovascular medication were randomised to receive either intensive evidence based dietary advice or 'usual' dietary advice. All participants continued to receive their usual medical care. The LOADD intervention resulted in an improvement in HbA1c that was significantly greater that shown in the control group at six months (−0.4%, 95% confidence interval −0.7% to −0.1%, p=0.007) as well as greater improvements in weight, BMI and waist circumference. This research indicates that intensive dietary advice can appreciably improve glycaemic control and anthropometric measures in individuals with type 2 diabetes and unsatisfactory HbA1c even when hypoglycaemic drug treatment is optimal. More information.

Ngati and Healthy Study
Ngati and Healthy, the 2006 Whanau Ora Award supreme winner (Read the media release here) and a 2006 Health Innovation Award finalist, is a collaborative community intervention between Ngati Porou Hauora and the Edgar National Centre for Diabetes Research, aimed at reducing the incidence of insulin resistance in the short term and type 2 diabetes in the long term. Implementation of the diabetes prevention community intervention began in 2004. More information

Insulin Resistance

Although type 2 diabetes is a heterogenous condition, resistance to the action of insulin is believed to be the underlying abnormality in the majority of cases. Because of its association with hypertension, dyslipidaemia, obesity and hyperuricaemia, insulin resistance is believed to be an important determinant of the global problem of cardiovascular disease.

If the epidemic proportions of type 2 diabetes are to be reversed, it seems imperative that serious attempts to reduce the risk of such should be made before the onset of Impaired Glucose Tolerance, at a stage when only insulin resistance is apparent (the first identifiable abnormality). Lifestyle factors are known to be important in the development of insulin resistance and type 2 diabetes, however many important questions remain unanswered.

The Dynamic Insulin Sensitivity and Secretion Test

Currently the most accurate methods for measuring insulin sensitivity are the 'gold-standard' euglycaemic clamp and the intravenous glucose tolerance test, which are complicated and expensive and can only be used in small research trials. For larger population-based studies crude surrogates are available to measure insulin sensitivity (most are based on fasting insulin and glucose). We have recently developed a new, dynamic, 30-minute test developed from our clinical model-based glucose and insulin control trials. This model's clinical accuracy is vastly superior to those described previously and has been compared (under simulated conditions) with 146 euglycaemic clamp tests, where it has performed remarkably well.

This test (called the Dynamic Insulin Sensitivity and Secretion Tests (DISST)) has been validated against the gold standard euglycaemic clamp test in a new population (See abstract of publication). It has proved relatively easy to perform, is relatively inexpensive and reliable, and it could be used in large research studies of individuals at high risk of diabetes and cardiovascular disease. We believe DISST could potentially be used in clinical practice and would be of major international importance given the increasing numbers of individuals at risk of diabetes and heart disease. More Information.

Does nutrient composition influence insulin sensitivity?

There is considerable evidence to show that weight loss can improve insulin sensitivity in individuals with insulin resistance or at risk of diabetes and CVD but very few studies have examined the effect of macronutrient composition on direct measures of insulin sensitivity. Thus we compared the effects of dietary advice including moderate increases in protein and fibre without specifying energy intake with standard low-fat, high-carbohydrate dietary recommendations on insulin sensitivity and secretion. Women at risk of diabetes were randomised to either a standard diet that was intended to be low in fat and relatively high in carbohydrate or to a relatively high protein (up to 30% of energy), relatively high fibre (>30g/day) diet for 10 weeks. Advice regarding strict adherence to energy intake goals was not given. Insulin sensitivity and secretion was assessed by DISST. In contrast to the improvements in body composition and metabolic risk factors on the high protein, high fibre diet, insulin sensitivity was reduced in comparison with the standard diet. Basal insulin secretion and fasting plasma glucose also appeared to be reduced, and first phase insulin secretion was increased on this diet (More information).

Obesity

The obesity epidemic is a worldwide phenomenon and New Zealand has one of the highest rates of obesity. Results from the 2008/09 Adult Nutrition Survey (Ministry of Health, 2011) indicate that the 28% of adult New Zealanders are now obese and two thirds are over weight or obese. The prevalence of obesity is even higher in our Maori and Pacific communities with estimates of 45% and 59% respectively. As obesity greatly increases the risk that an individual will develop diabetes, cancer and cardiovascular disease understanding the factors which influence obesity and exploring approaches to reducing and preventing obesity is a key focus of our research.

APPLE (A Pilot Programme for Lifestyle and Exercise) Study
A 2-year school-based environmental intervention to reduce childhood obesity

Body Composition in Relation to Ethnicity
Comparing body composition and measures of comorbidities in those of Maori and European ethnicity to determine whether the international BMI cut-off for overweight and obesity should be applied to the Maori people of New Zealand.

HEAT (Healthy Eating And Training) Study
A 2 x 2 randomised controlled trial comparing two dietary interventions and two support programmes and their effectiveness on weight maintenance

MInT: Motivational Interviewing in Treatment
A randomised controlled trial involving 4-8 year old overweight children and their families to determine how best to inform parents that their child is overweight in a manner that increases acceptance of that information and produces appropriate behaviour change

Play Study
To determine the reliability of measuring the number of permanent play facilities in a school playground, and whether this is related to physical activity in children

POI: Prevention of Overweight in Infancy
A randomised controlled trial aimed at determining if extra guidance and support around sleeping, eating and physical activity during infancy can reduce the rate of excessive weight gain in the first three years of life

TV Study
To determine the impact of removing TVs for 4 weeks in order to assess the effects on family functioning/interaction and to find out how families dealt with no TV in their home

The Obesity Epidemic - video

A video featuring Professor Jim Mann which puts the obesity epidemic in the spotlight