Diabetes in Older Adults
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1 Diabetes in Older Adults NICOLAS MUSI, MD Barshop Institute for Longevity and Aging Studies San Antonio GRECC University of Texas Health Science Center San Antonio, TX
2 Metabolic Alterations in Aging Sarcopenia Muscle Mass Strength Quality Altered Brain Metabolism (AD) Dyslipidemia CV Disease Low Bone Mineralization Type 2 DM Obesity
3 Incidence (per 1,000) of major diabetes complications among adults with diabetes, by age, Jeffrey B. Halter et al. Diabetes 2014;63:
4 Percent of Population Prevalence of Type 2 Diabetes, Undiagnosed Diabetes, and IGT Age (years) Impaired Glucose Tolerance (Prediabetes) Undiagnosed Type 2 Diabetes Diagnosed Type 2 Diabetes Adapted from Harris MI. Consultant 1997;37(Suppl):S9.
5 One in every two people age 65 and older have diabetes or pre-diabetes
6 Why Diabetes Risk Increases With Age?
7 Type 2 Diabetes in Aging b Cell Failure Insulin Resistance Low Physical Act. Sarcopenia Decreased Insulin Action Visceral Adiposity
8 Effect of Age on Insulin Secretion Young Older Normal Glucose Tolerant Old Impaired Glucose Tolerant Pancreas Blood Glucose (mg/dl) Insulin (mu/ml) Time (min) Time (min)
9 Metabolic Signaling Pathways in Aging Glucose Insulin TLR4 TNF-R Fatty Acids P P IRS P Ribosome (Synthesis) P mtor Ub P Akt P MuRF1 Atrogin IKK-NFkB ROS Lipids Ub Mitochondrial Dysfunction Proteasome (Breakdown)
10 mg/kg-ffm.mim Effect of Age on Insulin Sensitivity 8 7 Insulin Sensitivity (M) (27 years) 6 5 (70 years) Young BMI=23.8 Older BMI=25.1 Petersen, Science, 2003
11 Percent Effect of Age on Lipid Content Magnetic Resonance Spectroscopy Intramyocellular Lipid Content (70 years) EMCL-CH (27 years) IMCL-CH EMCL-CH 3 IMCL-CH Young Older PPM Petersen, Science, 2003
12 ATP synthesis rate (nmol/mg protein/min) Effect of age on Mitochondrial ATP Production 80 Younger Older 60 * * 40 * * 20 * Luciferase assay (ATP synthesis rate) 0 Mitochondria Alone Succ + Rotenone Glutamate + Malate Pyruvate + Malate *P<0.05 vs. older group.
13 ATP synthesis rate (nmol/mg protein/min) Effect of aerobic exercise on Mitochondrial ATP production in older subjects Before exercise After exercise * * Level in Young 40 * 20 0 Mito alone S + R G + M P+ M S+R: Succinate + Rotenone; G+M: Glutamate + Malate; P+M: Pyruvate + Malate *, P<0.05 vs. older group before exercise.
14 Factors involved in mitochondrial biogenesis PGC-1 b a g AMPK NUCLEUS NRF1 TFAM TFAM mtdna mrna MITOCHONDRIA Mitochondrial biogenesis Modified from Vina et al Adv Drug Del Rev. 2009
15 Plasma endotoxin (EU/ml) LPS Concentration in Aging Younger Older * Ghosh et al, J Geron (2014)
16 Intestinal Barrier Dysfunction and Aging Rera, PNAS (2012) Intestinal Barrier Dysfunction Predicts Death
17 How should older adults be treated for diabetes?
18 Recommendations (ADA, AGS) Goals of Treatment (Tight Control?) Consider: 1) Functional Status 2) Life expectancy 3) Cognitive Function 4) Clinical Heterogeneity (prone to complications?)
19 Does every diabetic person develops (mv) complications? No approximately 20-40% How long does it take to develop (mv) diabetic complications? 15 years, on average How much does the A1c level matter? It matters a lot
20 How long does it take to develop diabetic complications?
21 How much does the A1c level matter?
22 Kaplan-Meier Survival Curves by Frailty Status Not Frail Frail Time, Days Espinoza, Hazuda (SALSA) Not Frail Frail Pre-Frail
23 Recommendations (ADA, AGS) Goals of Treatment (Tight Control?) Functional, Cognitively Intact, Significant Life Expectancy: - Similar Goals as Younger Person - A1c ~ 7%
24 Recommendations (ADA, AGS) Goals of Treatment (Tight Control?) Decreased Function/Cognition, Short Life Expectancy: - Glycemic Control can be Relaxed - Avoid Hyperglycemic Complications!
25 Antihyperglycemic therapy T2DM (ADA Standards, 2016)
26 Remaining Questions About DM in Older Adults - Epidemiology of diabetes and complications - Etiology - Screening and diagnosis - Preventative strategies (lifestyle and pharmacological) - Treatment goals, target, and interventions - Clinical trials for prevention and treatment - DM complications Halter et al, Diabetes Aug;63(8):
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