By Dr. Geoffrey Modest
The Am Heart Assn and Am Diabetes Assn just published joint guidelines regarding the prevention of cardiovascular disease, by far the greatest killer in diabetics (see dm prev CVD ada2015 in dropbox, or DOI: 10.2337/dci15-0012). Given the sometimes discordant recommendations of the different organizations in the past, this is a positive approach. Details:
Lifestyle management of diabetes
- Physical activity: studies confirm that exercise is associated with weight loss, increased HDL levels, and decreased A1c. One large study (Look AHEAD) did not find fewer cardiovasc events with exercise, but the exercising group did take fewer cardioprotective drugs (i.e., exercise seemed to decrease the use of meds)
- Nutrition: the Mediterranean diet in a Spanish study found a 30% decrease in CVD events (see for more detailed review: https://stg-blogs.bmj.com/bmjebmspotlight/2014/01/21/primary-care-corner-with-geoffrey-modest-md-mediterranean-diet-and-cad-primary-prevention/ ). Some but not all data support a low glycemic index diet for improving A1C levels and lowering triglycerides, which is commonly elevated in diabetics esp if not in good control [other approaches to lowering TG levels include decreasing alcohol intake, exercise, losing weight and decreasing saturated and trans fats (which lower HDL and raise TG) and substituting monounsats and polyunsats].
- Weight management: diet and exercise, as above, but much more successful in structured programs with monitoring the lifestyle changes, calorie reduction (including through meal replacements as done in studies), counseling, patient self-monitoring with frequent weight assessments. The studies finding the most weight loss tended to be those with the most intensive interventions (including motivational interviewing, intensive counseling, goal setting/contracts, refresher courses, incentives to those who lose the most weight…). One issue mentioned is whether the weight gain associated with smoking cessation might lead to increased CVD mortality: an observational study found that even the mean weight increase of 3.6 kg had better outcomes than continued smoking.
- Pharmacological therapy for weight loss (I don’t use these meds, but will provide their review): the Obesity Society suggests that meds are indicated in those with BMI>30 or if 25-30 with medical co-morbidities. One should always promote the lifestyle changes, though these are often hard for patients to maintain long-term, and also to avoid drugs that increase weight, such as several antiepileptics, diabetic drugs (e.g. thiazolidinediones, insulin, glinides, and sulfonylureas cause weight gain; metformin and GLP-1 agonists produce weight loss on the order of 5%), many psych meds. Only 3 drugs are approved for long-term (orlistat, lorcaserin, and extended-release topiramate/phentermine), the rest (including regular phentermine alone) are mostly approved for <12 weeks only.
- Surgery (mostly now called “metabolic” instead of “bariatric” surgery since there are pretty profound metabolic improvements even before large weight changes): the guidelines vary some (International Diabetes Federation in 2011 recommended surgery for BMI >30 if diabetic patients not able to reach diabetic goals with meds, esp if comorbidities present), but the new AHA/ACC/Obesity Society guidelines stick to the BMI 35 cutoff for those with obesity-related comorbidities such as diabetes. The best long-term data come from the Swedish Obese Subjects (SOS) study at 15 years: weight loss as % of total body weight was 27% for gastric bypass, 18% for vertical-band gastroplasty and 13% of gastric banding (will append my blog for the SOS study at the bottom). The metabolic improvements with “metabolic” surgery are pretty profound: 78% have resolution of diabetes (though data are from meta-analysis of short-term studies, though SOS did find 72% remission at 2 years and 36% at 10 years). Also 78% risk reduction in development of diabetes. Also 63% improvement in hypertension, 65% in hyperlipidemia. Some retrospective data show that nephropathy may be reversed with surgery. And most studies find decrease in CVD as well as all-cause mortality. Complications of the surgery are uncommon, other than nutrient deficiencies.
- Aspirin: the data are pretty mixed. basically, there “may be” a modest effect of aspirin in diabetic patients, on the order of a 9% risk reduction which in a meta-analysis was statistically non-significant, but with a >2-fold increase in GI bleeding, leading to the tepid recommendation: low-dose aspirin (75-162 mg) is “reasonable” in those with 10-year CVD risk >10% and no increased risk of bleeding, and (per “expert opinion”) in those with risk of 5-10% risk [note: several years ago this was a strong recommendation, which was down-graded by ADA when the POPADAD trial came out (diabetic patients with documented PAD), finding a trend to less cardioprotection with aspirin (see org/10.1136/bmj.a1840)]
- Target A1C: <=7% for most patients (to reduce microvascular complications), <6.5% in younger people without CVD and shorter duration diabetes, 8% or even slightly higher in those with history of severe hypoglycemia, limited life expectancy, cognitive impairment repeated counseling.
- Diabetic meds: metformin is still king.
- Hypertension: the JNC8 goals are supported: <140/90 for most individuals. Lower targets may be appropriate for some individuals “although the guidelines have not yet been formally updated to incorporate this new information” and seem to include younger patients who can achieve systolic <130 without undue treatment burden. They do note that the 2015 ADA goal is currently <130/80 if this goal can be achieved safely. ACE/ARB should be used.
- Lipids: the efficacy of statins is similar in diabetics and nondiabetics, with a 39 mg/dl (1 mmol/L) decrease in LDL being associated with a 21% decrease in major vascular events and a 9% decrease in total mortality, and statins work similarly independent on the baseline LDL. Recommendations: check the lipid level at least annually. Continue to emphasize lifestyle changes. These guidelines are similar to the ADA guidelines for the past few years: all diabetics between 40-75 yo and with LDL from 70-189 should be on a moderate-intensity statin. Those at higher risk should be on a high-intensity statin. If <40 or >75 yo, individualize therapy.
- Screening for renal and cardiovasc complications: note that proteinuria and/or decreased GFR are associated with increased cardiovasc and total mortality. So, check annual microalbuminuria and creatinine/eGFR. In terms of cardiovascular screening, they feel that EKGs are reasonable (given that up to 20% of diabetics have abnormalities, those with abnormalities have a higher all-cause mortality, so the EKG might help in risk stratification — which, to me, means that those with abnormal EKGs we should be more aggressive in risk factor reduction, including more aggressive lipid lowering. It is unclear that there is benefit to pursuing EKG changes with more invasive testing/treatment, since there are no studies showing improved outcomes in asymptomatic diabetics with EKG changes. The guidelines do consider it “reasonable” to measure ABIs in asymptomatic diabetics (a marker of generalized atherosclerosis, which would lead to more aggressive risk factor modification), coronary artery calcium scoring by CT scanning (which is more often positive in diabetics, though a “0” score effectively precludes cardiovascular events over 5 years). They also feel it is reasonable to do stress myocardial imaging in those with the highest CAC scores (>400), given the high rate of cardiovascular events (though no RCTs on this)
Comments:
- The A1C goals they suggest are mostly reasonable, as I argue in the blog https://stg-blogs.bmj.com/bmjebmspotlight/2015/06/25/primary-care-corner-with-geoffrey-modest-md-tight-diabetes-control-and-cardiovasc-disease-followup-of-the-va-study/. However, I do have several patients where it is dangerous (I think) to lower the A1C even to 10% — they are cognitively limited, unable to stick to diet despite many interventions including home care and senior day programs, are on very high dose insulin, metformin and exanitide, and have blood sugars in the 45 to >500 range with A1c in the 12% range. For them, I cannot just ramp up the insulin (real risk of hypoglycemia, which by itself confers a risk of ischemic and other cardiac events, including increases in blood pressure, heart rate, myocardial contractility, arrhythmias, ischemic EKG changes, endothelial dysfunction, platelet reactivity, inflammatory mediators…) and, bottom line, I need to treat the patient and not the A1C
- The new meds: I am really hesitant to use new meds just based on lowering A1C levels, a surrogate marker. We have seen too many drugs (e.g. rosiglitazone) which by my reading of the literature is a harmful drug. And the new DPP-4 inhibitors seem to be clinically lackluster (see https://stg-blogs.bmj.com/bmjebmspotlight/2015/06/24/primary-care-corner-with-geoffrey-modest-md-dpp-4-inhibitors-and-cardiovascular-outcomes/ ). The FDA does allow diabetes meds to be marketed just for lowering A1C levels, though it is good that they now request evidence that there is no increase in cardiovascular risk by the meds. But, bottom line: I really need to see pretty solid evidence that a new drug does more than just lower A1c levels (and doesn’t create more problems) before I will use them. Of note, the PROactive trial of pioglitazone, which I do use infrequently, did find a 16% decrease in their secondary outcome of MI, stroke and cardiovasc mortality.
- Hypertension: I still use a lower target for blood pressure control in diabetics (e.g. 130/80) but am very concerned in the elderly or those with longstanding diabetes in terms of autonomic dysfunction and orthostatic hypotension (which I check for regularly in the office). And I am much less aggressive in blood pressure lowering if I really need to flog the patients with lots of meds to do so. For a fuller review including a large meta-analysis of blood pressures achieved and outcomes, as well as a critique of JNC 8, see https://stg-blogs.bmj.com/bmjebmspotlight/2015/03/06/primary-care-corner-with-geoffrey-modest-md-blood-pressure-goals-in-diabetics/ and https://stg-blogs.bmj.com/bmjebmspotlight/2013/12/22/primary-care-corner-with-dr-geoffrey-modest-jnc-hypertension-guidelines-simple-goals/ . Though I do preferentially use ACE/ARB in diabetics (they may, in some but not all studies, prevent the development of diabetes), I am not aware of any good data showing that this is beneficial in those without evidence of any renal disease.
- Screening and lipids: I am pretty aggressive in lipid management of my diabetics (80% of diabetics die from cardiovasc disease). I still adhere to the treat-to-goal philosophy, so in my diabetics who have any other significant risk factor, I use only high potency statins (except in rare cases where the lipids are already really good, then I still use lower dose statins, since trials have found that lowering LDL from 96 to 70 is as useful as lowering from 130 to 100. But I do have a few patients with baseline LDLs under 100 and given atorvastatin 10-20 mg brings it down to 50). But my target overall is to try to get below 70 if possible, with escalating the statins to rosuvastatin 40 if needed. See a recent blog for more info on CAC scoring and my concerns about the 2013 AHA/ACC guidelines: https://stg-blogs.bmj.com/bmjebmspotlight/2015/08/05/primary-care-corner-with-geoffrey-modest-md-comparison-of-the-2013-accaha-lipid-guidelines-to-atpiii/
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