10/11/19 Disclosure New Frontiers in Diabetes Management: - PDF document

10/11/19 Disclosure New Frontiers in Diabetes Management: Challenges in I have no relevant financial relationships with any company the care of Asian Patients related to the content of this course UCSF 8 th Annual Asian Health Symposium 2019 T ejaswi Kompala, MD UCSF Division of Endocrinology 1 2 Roadmap • In China, diabetes prevalence increased from 1% in 1980 Asia is considered as • Diabetes epidemiology to 9.7% in 2010. the epicenter of • Pathophysiology differs in Asians • In Korea, rates increased recent worldwide • Metabolic Phenotype from 0.9% in 1971 to 9.9% in • Diagnosis and T esting epidemic of diabetes 2009. • Treatment: Lifestyle Interventions These prevalence rates equal that of the US: CDC report estimates that 9.4% of Americans have diabetes. Number of People with Diabetes in 2017 and 2049 (20-70 years old) IDF Diabetes Atlas 8e 3 4 1

10/11/19 352 million people Half of people with are at risk diabetes don’t know of developing type they have it 2 diabetes Undiagnosed percentage and undiagnosed cases of diabetes Number of adults (20-79 years) with Impaired Glucose T olerance in 2017 (20-79 years) per region IDF Diabetes Atlas 8e IDF Diabetes Atlas 8e 5 6 Under-Recognition of Diabetes Among Asian Incidence of Diabetes Among US Ethnic Subgroups Americans DISTANCE: 15,357 new cases of medically diagnosed diabetes in 2010 % of NHANES participants UNAWARE of Diabetes Diagnosis 50.9 49 36.8 32.3 Whites Blacks Hispanics Asians JAMA. 2015;314(10):1021-1029 Karter AJ et al. Dia Care 2013 7 8 2

10/11/19 The Pathophysiology Of Diabetes Differs In Asian Patients How Does Diabetes • Proposed mechanism: insulin resistance, initial pancreatic beta cell compensatory response, and eventual beta cell exhaustion. Differs In The Asian Patient: Implications For Reduced insulin secretory capacity, especially in the early Diagnosis And phase, has been reported not only in Japanese but also in other East Asians Treatment such as Korean and Chinese. Yabe D., eat al. Current Diab Reports. 2015; Qian L., et al. Diabetes Metab Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), Res Revi 2009; Kim DJ et al. Metabolism. 2001, Fukushima M. et al. Diabetes Res Clin Pract . 2004 and type 2 diabetes mellitus (DM). 9 10 HOMA-IR Is Lower In Japanese Throughout NGT , IGT , And T2DM in Comparison With that of Caucasian The insulinogenic index , a marker of beta cell function that measures insulin and glucose levels, was lower for Japanese subjects with normal glucose tolerance Fukushima M. et al. Diabetes Res Clin Pract . 2004 Fukushima M. et al. Diabetes Res Clin Pract . 2004 11 12 3

10/11/19 DM2 Physiology: Take Home Points Diabetes in Asians • Younger Age 1. Counterbalance between insulin secretion and insulin • Lower body-mass resistance is critical for T2DM pathogenesis index (BMI) 2. Why Asians show a low reserve capacity of insulin secretion? • But…INCREASED visceral adiposity 3. GWAS studies are trying to answer this question: several T2DM-susceptible genes in East Asians but it is difficult to know how these genes might affect β cell function. Yasuda K, et al. Nat Genet. 2008; Cho YS, et al. Nat Genet. 2012 13 14 BMI is lower in Asians vs. Non-Asians with Diabetes Lower BMI, Higher Body Fat In Asians • NYC healthy volunteers: 445 Whites, 243 Asians (mostly Chinese and foreign born) White Males Asian Males White Females Asian Females BMI kg/m2 25.1 23.4 23.9 22.5** Body Fat 19.3% 21.4%* 30.1% 31.6% (DXA) BMI of Asians with diabetes outside of US is < 25 *p=0.006 white vs. Asian males; **p=0.002 white vs Asian females • Skinfold measurements: Significantly higher fat in trunk and arms in Asians compared to whites Wang J. eta l. Am J Clin Nutr 1994 Karter AJ et al. Dia Care 2013 15 16 4

10/11/19 BODY FAT DISTRIBUTION MIGHT ACCOUNT FOR THE DIFFERENCES IN T2DM RISK IN ASIAN GROUPS. Alba, D. et al., JECM 2018; John Shepherd; UCSF Nutrition and Obesity Research Center ( NORC) 17 19 Fat Distribution Is A More Precise Predictor Of T2D Asians Have High Visceral Adiposity White Black Asian Hispanic Filipino White African American Those who expand both visceral (n=181) (n=196) (n=193) and subcutaneous fat mass BMI, kg/m2 25.5 * 26.0 29.7 † Percent with T2D develop T2D at relatively high BMI Type 2 Diabetes 32.1% *‡ 5.8% 12.1% Waist-hip ratio 0.84 *‡ 0.78 0.82 † Those who preferentially expand VAT by CT (cm3) 69.1 * 62.3 57.5 † visceral adipose tissue (VAT) mass, develop T2D at a lower BMI *p<0.05 Filipino vs. African American Normal weight Overweight Obese †p<0.05 African American vs. white VAT accrual is tightly linked to T2D risk ‡p<0.08 Filipino vs. white Obesity Research Volume 13, Issue 8, pages 1458-1465, 6 SEP 2012 DOI: 10.1038/oby.2005.176 http://onlinelibrary.wiley.com/doi/10.1038/oby.2005.176/full#f1 Shai et al. , Diabetes Care 2006; Thorpe et al., Diabetes Care 2009 20 21 5

10/11/19 T wo Possible Mechanisms Could Drive Visceral White Adipose Tissue (Wat) Expansion And Consequent Insulin Resistance And T2D Genetics + lifestyle Subcutaneous WAT (scWAT): • Minimal inflammation • Relatively insulin sensitive • Highly thermogenic “Beige”. ( Determining How Fat Tissue ( Accumulation Affects Metabolic Disease Visceral WAT (vWAT): Type 2 diabetes Requires Understanding How Fat Mass • Prone to inflammation • Drives insulin resistance is Regulated • Increases risk for T2D , cardiovascular disease, and mortality Insulin Resistance 23 26 Fasting blood glucose and HbA1c are the primary tests in the diagnosis of diabetes • Gold standard oral glucose tolerance test (OGTT) is not traditionally recommended by the ADA. • In 2010 in China: 44% of men and 50.1% of women with diabetes had Diagnosis and normal fasting glucose ( implying normal insulin sensitivity ) but T esting in Asian isolated increased two-hour blood glucose ( from beta-cell Patients dysfunction ) Yang W. et al. N Engl J Med. 2010; Bao Y. et al. Br. Med. J. 2010 28 29 6

10/11/19 HbA1C threshold of 6.3% was highly specific for detecting undiagnosed diabetes Characteristics Curve Of Hba1c For Detecting Diabetes At Each Possible Hba1c Threshold. The selection of diagnostic tests and cutoff values used in the US should be modified for Asian patients, especially Diagnosis and given that normal fasting glucose levels T esting in Asian may mask diabetes that would be found Patients using an oral glucose challenge test. Yuqian Bao et al. BMJ 2010;340:bmj.c2249 30 31 The Cornerstone Of Treatment For T ype 2 Diabetes Is Lifestyle Intervention, Including Dietary Modifications: Diabetes Risk According T o Dietary Intake Implications For Treatment in Asian Patients Hu F. Dia Care 2011 32 33 7

10/11/19 The Cornerstone Of Treatment For T ype 2 Diabetes Is Lifestyle Intervention, Including Dietary Modifications: Diabetes Risk According T o Dietary Intake Effect of transitioning Asian Americans and Caucasian Americans from a Fiber Unsaturated: Saturated Fat traditional Asian diet to a traditional Western diet (TWD) Risk adjusted for: • BMI • Exercise • Family history Asian Diet : 70% CHO, 15% protein, • Alcohol 15% fat, and 15 grams of fiber/1000 kcal TWD : 50% carbohydrate, 18% protein, 34% fat, and 6 grams of fiber/1000 kcal. Trans Fat Glycemic Load Hu F. Dia Care 2011 Hsu W C at al. PLOS ONE 2014 34 37 AA Transitioned to Western Diet: Elevated Body Fat Weight Loss And Improved Insulin Sensitivity In Both And Trunk Fat With A Rise In Insulin, Despite Groups On Traditional Asian Diet Insignificant Weight Gain Hsu W C at al. PLOS ONE 2014 Hsu W C at al. PLOS ONE 2014 38 39 8

10/11/19 CA transitioned to TWD: significantly increased weight, body fat, and trunk fat with no significant change in A little weight loss and exercise = big benefits insulin resistance • U.S. Diabetes Prevention Program • 2000+ Pre-diabetic subjects with BMI >24 (or >22 if Asian) • Randomized to Metformin, Intensive Lifestyle, or Routine Care • Intensive lifestyle: • 7% Body weight loss (low fat, low calorie diet) • 150 minutes per week of moderately strenuous activity Macronutrient composition of Asian diet improved insulin sensitivity in both AA and CA. In contrast, TWD may have impaired the insulin sensitivity in AA, but not CA with normal BMI, raising the possibility that diets may elicit different effects in different ethnic groups . N Engl J Med 346:393-403, 2002 Hsu W C at al. PLOS ONE 2014 40 44 Diabetes Prevention Program Chinese Diabetes Prevention Study 92% completion rate • 577 Chinese adults with pre-diabetes, mean age of 40 and BMI of 26 • Randomized to: • Diet (Consume more vegetables and less sugar and alcohol. If overweight, eat less) • Exercise (increase leisure physical activity) • Diet + Exercise Lost 7% body weight with diet • Control and moderate exercise N=3234 NNT Lifestyle: 6.9 people x 3 yrs NNT Metformin 13.9 people x 3 yrs N Engl J Med 2002 45 46 9