Ulf Smith, MD Sahlgrenska University Hospital, Gothenburg, Sweden - - PowerPoint PPT Presentation
Asian Chapter Asian Chapter Achieving glycemic control: What are the management options for the next decade Ulf Smith, MD Sahlgrenska University Hospital, Gothenburg, Sweden Algorithm for the metabolic management of type 2 diabetes;
Asian Chapter
Asian Chapter
Algorithm for the metabolic management of type 2 diabetes; Reinforce lifestyle interventions at every visit and check A1C every 3 months until A1C is <7% and then at least every 6 months. Nathan D M et al. Diabetes Care 2009;32:193-203
Nathan D M et al. Diabetes Care 2009;32:193-203
Nathan D M et al. Diabetes Care 2009;32:193-203
50-80 % of deaths in people with diabetes are due to cardiovascular disease (CVD) Most important are: Coronary heart disease
Cerebrovascular disease
diabetes Peripheral vascular disease
people with diabetes vs. general population
1 % increase in HbA1c
nephropathy
Refs Ann Intern Med 141:421, 2004 Diabetologia 48:1749, 2005 BMJ 321:405, 2000
Red blood cell Sugar Low HbA1c High HbA1c
Microvascular disease – clearly related to glucose/HbA1c levels and intensified control reduces risk (DCCT, UKPDS, ADVANCE etc) Macrovascular disease – more controversial and less clear. Postprandial glucose levels better predictors than fasting glucose levels. But the postprandial state is complex also reflecting, for instance, postprandial lipid levels/elimination
Axelsen M et al. Ann Intern Med 131:27-31, 1999
Table 25 Recommendations for treatment of dyslipidaemia in diabetes
Recommendations Classa Levelb Refc In all patients with type 1 diabetes and in the presence of microalbuminuria and renal disease, LDL-C lowering (at least 30%) with statins as the first choice (eventually drug combination) is recommended irrespective of the basal LDL-C concentration. I C In patients with type 2 diabetes and CVD or CKD, and in those without CVD who are over the age of 40 years with
mmol/L (less than ~70 mg/dL) and the secondary goal for non-HDL-C is <2.6 mmol/L (100 mg/dL) and for apo B is <80mg/dL. I B 15, 16 In all people with type 2 diabetes LDL-C <2.5 mmol/L (less than ~100 mg/dL) is the primary target. Non-HDL-C <3.3 mmol/L (130 mg/dL) and apo B <100 mg/dL are the secondary targets. I B 15, 16
a Class of recommendation. b Level of evidence. c References.
apo = apolipoprotein; CKD = chronic kidney disease; CVD = cardiovascular disease; LDL-C = low-density lipoprotein-cholesterol. ESC/EAS Guidelines
Recommended treatment targets for patients with diabetes and CAD (modified from the European Guidelines for Cardiovascular Disease Prevention)
Eur Heart J 28:88-136, 2007
Peter Gæde, M.D, D.M.Sc., Henrik Lund-Andersen, M.D, D.M.Sc., Hans-Henrik Parving, M.D, D.M.Sc., and Oluf Pedersen, M.D, D.M.Sc. 358:580-591, 2008
N Engl J Med 358:580-591, 2008
The Action to Control Cardiovascular Risk in Diabetes Study Group Methods In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary
nonfatal stroke, or death from cardiovascular causes. The finding
discontinuation of intensive therapy after a mean of 3.5 years of follow-up.
N Engl J Med 358:2545-59, 2008
As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2
Institute; ClinicalTrials.gov number, NCT00000620.)
N Engl J Med 364:818, 2011
The NEW ENGLAND JOURNAL of MEDICINE
ORIGINAL ARTICLE
Shari Bolen, MD, MPH; Leonard Feldman, MD; Jason Vassy, MD, MPH; Lisa Wilson, BS, ScM; Hsin-Chieh Yeh, PhD; Spyridon Marinopoulos, MD, MBA; Crystal Wiley, MD, MPH; Elizabeth Selvin, PhD; Renee Wilson, MS; Eric B. Bass, MD, MPH; and Frederick L. Brancati, MD, MHS
147:386-399, 2007
Data Sources: The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception through January 2006 for original articles and through November 2005 for systematic reviews. Unpublished U.S. Food and Drug Administration and industry data were also searched. Study Selection: 216 controlled trials and cohort studies and 2 systematic reviews that addressed benefits and harms of oral diabetes drug classes available in the United States.
147:386-399, 2007
Weighted mean difference in blood pressure, laboratory values, and body weight with use of oral medications for type 2 diabetes mellitus
147:386-399, 2007
147:386-399, 2007
Weighted mean difference in blood pressure, laboratory values, and body weight with use of oral medications for type 2 diabetes mellitus
147:386-399, 2007
Weighted mean difference in blood pressure, laboratory values, and body weight with use of oral medications for type 2 diabetes mellitus
Bunck M C et al. Diabetes Care 2011;34:2041-2047 β-Cell function parameters during 3 years of EXE (n = 16) and GLAR (n = 20) treatment
Figure 3a. Mean (±SE) change from baseline to week 16 in HbA1c. Baseline values PBO 6.6%, ALO 6.8%, ALO/PIO 6.6%. P-values for the LS mean treatment difference compared with PBO. White bars, PBO; grey bars, ALO; dark grey bars, ALO/PIO.
P<0.001 P<0.001
0,4
0,0 0,5 1,0
Change in A1c (%)
Placebo ALO 25 mg ALO 25 mg+PIO 30 mg
2 4 6 8 10 12 14
1 2 3 4 5 6 7 8
GLP-1 (pmol/L) Time (h)
Placebo ALO 25 mg ALO 25 mg +PIO 30 mg
Figure 4a. Mean (±SE) postprandial active GLP-1 at week 16. P-values for the LS mean treatment difference compared with PBO: * <0.05, ** <0.01, *** <0.001. White triangles, PBO; grey triangles, ALO; black triangles, ALO/PIO.
** *** *** *** *** *** ** * ** * ** *
5 10 15 20 25
1 2 3 4 5 6 7 8
Glucagons (ng/L) Time (h)
Placebo ALO 25 mg ALO 25 mg +PIO 30 mg
Figure 4b. Mean (±SE) postprandial glucagon at week 16. P-values for the LS mean treatment difference compared with PBO: * <0.05, ** <0.01, *** <0.001. White triangles, PBO; grey triangles, ALO; black triangles, ALO/PIO.
** *** *** *** *** ** ** ** *** * ** ** ***
1 2 3 4 5
1 2 3 4 5 6 7 8
Triglycerides (mmol/L) Time (h)
Placebo ALO 25 mg ALO 25 mg +PIO 30 mg
Figure 2a. Mean (±SE) postprandial triglycerides at week 16. P-values for the LS mean treatment difference compared with PBO: * <0.05, ** <0.01, *** <0.001. White triangles, PBO; grey triangles, ALO; black triangles, ALO/PIO.
** *** *** *** *** *** *** *** *** *** ** ***
0,0 0,2 0,4 0,6 0,8 1,0
1 2 3 4 5 6 7 8
Chylomicron Triglycerides (mmol/L) Time (h)
Placebo ALO 25 mg ALO 25 mg +PIO 30 mg
Figure 2b. Mean (±SE) postprandial chylomicron triglycerides at week 16. P-values for the LS mean treatment difference compared with PBO: * <0.05, ** <0.01, *** <0.001. White triangles, PBO; grey triangles, ALO; black triangles, ALO/PIO.
* ** *** *** *** *** *** *** *** ***
0,5 1 1,5 2 2,5 3
1 2 3 4 5 6 7 8
VLDL1 Triglycerides (mmol/L) Time (h)
Placebo ALO 25 mg ALO 25 mg +PIO 30 mg
Figure 2c. Mean (±SE) postprandial VLDL1 triglycerides at week 16. P-values for the LS mean treatment difference compared with PBO: * <0.05, ** <0.01, *** <0.001. White triangles, PBO; grey triangles, ALO; black triangles, ALO/PIO.
*** *** *** *** ** *** *** *** * *** **
available therapies?