VIEWS: 11 PAGES: 31 POSTED ON: 4/9/2011
Preventing and reversing type 2 diabetes Robert Schmidli Endocrinologist MB ChB, MRCP, FRACP, PhD Senior Staff Specialist, The Canberra Hospital Senior Lecturer, ANU Medical School www.schmidli.com.au Lecture outline Background Diabetes prevention Diabetes reversal Background History 1425 – “diabete” recorded in medical text 1675 – “mellitus” – sweet taste of urine 1889 – removal of pancreas in dogs Pre-1921 – diabetes uniformly fatal 1921 – treatment of diabetic boy with insulin derived from human pancreas Long-term complications Other milestones 1936 – type 1 distinct from type 2 diabetes 1942 – sulphonylureas for type 2 diabetes 1950s – biguanides (phenformin/metformin) 1960 – measurement of insulin 1993 – relationship between control and complications (1998 type 2) Definition of diabetes “Elevation of blood glucose due to an absolute or relative lack of insulin” Type 1 diabetes: Lack of insulin due to destruction of insulin-producing beta cells Type 2 diabetes: Complex multisystem condition Definition of diabetes and “pre- diabetes” Diabetes • Fasting > 7.0mmol/l • 2 hr after glucose > 11.1mmol Pre-diabetes Impaired glucose tolerance • 2 hr after glucose 7.8 – 11mmol/l Impaired fasting glucose • Fasting 5.6 – 6.9mmol/l What is insulin? Insulin Cell Receptor Defects in type 2 diabetes Reduced insulin Increased blood Pancreas production Blood glucose glucose levels Adipose tissue (fat) Liver Excessive glucose Muscle production from Resistance to action of liver insulin Adapted from Saltiel 1996, Jones 1999 Genetics “Single gene diabetes” (MODY) rare Strong inheritance Polygenic – involves multiple genes Risk in unaffected identical twin 90% Huge difference in ethnic groups despite same environment Lifestyle factors Inadequate exercise • Sedentary occupations • Automation • Long working hours Diet • Excess food available • Processed food Sleep disorders • Reduced sleep • Sleep apnoea (3x more common in diabetes) Progression of type 2 diabetes Obesity Pre- Diabetes Diabetes Insulin resistance diabetes (diet/tablets) (insulin-requiring) Insulin resistance Insulin production Time Diabetic complications Retinopathy Diabetes is the most common cause of visual loss Cardiovascular in Australian adults disease < 60 y.o. The most common cause of death in people with diabetes Nephropathy Diabetic Diabetes is a leading neuropathy cause of end-stage renal Foot ulcers, gangrene, disease amputations DOHW Report 1999 www.health.gov.au/internet/wcms/publishing.nsf/Content/health-pq-diabetes-pubs-diabetes99.htm Accessed November 29 2007. Diabetes in Australia AusDiab study • 42 randomly selected sites • 11,247 individuals tested Results • 7.5% of population ≥25y diabetic, 8.0% ♂, 7.0 ♀ • ≥ 75 years 23.6% diabetic • 50% undiagnosed • 30% high blood pressure or on treatment • 1/6 no physical activity, 50% 150 min/week • 1,000,000 Australians with diabetes • 60% overweight or obese, 2.5x that in 1980 • Number with diabetes has trebled since 1981 Drug treatment ↑ Insulin secretion • Sulphonylureas • GLP-1 analogues Insulin sensitisers • Metformin • “Glitazones” ↓ glucose absorption • Acarbose Insulin Diabetes prevention Diabetes/Prediabetes screening Age ≥50y Age ≥45 plus • Obesity (BMI 30 kg/m2) • First-degree relative with type 2 diabetes • Hypertension Aboriginal and Torres Strait Islanders ≥35 High-risk non–English-speaking ≥ 35y Impaired glucose tolerance/fasting glucose Clinical cardiovascular disease Women with previous gestational diabetes Obese women with polycystic ovary syndrome Diabetes Prevention Program USA study Over 3000 obese individuals with IGT Target: 7% weight loss 150 min/week exercise Compared to: • Metformin • Placebo (information on diet/exercise) Diabetes Prevention Program Reductions Metformin 31% Lifestyle 58% Problems with DPP Cost effectiveness Cost over 30 years: • Lifestyle intervention $62,600 • Metformin $35,400 • Delay until onset $24,500 Usefulness in “real life” Long-term adherence out of research project poor Drug prevention of diabetes Numerous drugs shown to reduce progression from pre-diabetes • Metformin • Sulphonylureas • Glitazones • Acarbose Benefit no greater than lifestyle May simply mask rise in blood glucose Risk probably reverts if drug stopped Huge numbers, costly Health benefits unknown Population health measures Advertising restrictions Education programs Media publicity Cost incentives/disincentives Limiting food types (eg schools) Exercise programs in schools/workplaces Few of these used to date Diabetes reversal Diabetes reversal No published evidence with standard lifestyle measures Prevention more important May occur with major lifestyle change Increased interest in surgical weight loss “Remission” not “Cure” • Normal blood glucose off medications Criteria for surgery Failed dietary/lifestyle management BMI ≥ 40 Other conditions (diabetes, sleep apnoea, joints etc) and BMI ≥ 35 Acceptable surgical risk Well motivated Restrictive procedures Laparoscopic adjustable gastric Vertical banded gastroplasty banding “lap-band” “stomach stapling” Roux-en-Y gastric bypass Other procedures “Cosmetic” procedures Apronectomy Fat usually reaccumulates Abdominoplasty High complication rate Liposuction No reversal of diabetes Not recommended Jejuno-ileal bypass “Desperate” cases Biliopancreatic diversion Seldom done in Aus Above + duodenal switch Complications Analysis of bariatric surgery 134 studies, 22,094 patients Mean ↓wt No patients (kg) Total population 7588 39.7 Gastric banding 482 28.6 Gastric bypass 2742 43 Gastroplasty 936 39.8 B/P diversion, duod switch 1282 46.4 Improvement in diabetes Complete FBG resolution HbA1C (%) (mmol/l) (%) Drop Drop Total population 76.8 2.4 3.9 Gastric banding 47.8 1.2 3.1 Gastric bypass 83.8 3 3.4 Gastroplasty 68.2 4.8 B/P diversion, duod switch 97.9 5.8 Conclusions Diabetes may be preventable and reversible Usually controlled rather than cured Lifestyle measures essential but unlikely to reverse diabetes Surgery useful in selected individuals Few attempts at population approach
"Preventing and reversing type 2 diabetes _PowerPoint_ - Robert "