Step up your diabetes game! We answer your questions from #MedTwitter. Returning guest, Jeff Colburn MD, FACP, FACE (USU) gives us a much needed diabetes update. Topics include: the pitfalls of A1C testing, the A1C target controversy, lifestyle interventions, continuous glucose monitoring, pathophysiology of type 2 diabetes (T2DM), use of SGLT2 inhibitors, GLP1 agonists, and how to initiate and titrate insulin therapy.
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Writer (including CME Questions) and Producer: Matthew Watto MD, FACP
Cover Art and Infographic: Bryan Brown MD
Hosts: Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP
Editor: Matthew Watto MD, FACP; Emi Okamoto MD
Guest: Jeff Colburn MD, FACP, FACE
Dr. Colburn mentions the following rough calculation: A1C of 6% = average glucose of 126 mg/dL. Add 30 mg/dL for every 1% increase in A1C (e.g. 7% = average glucose 156 mg/dL and so forth).
When adding an SGLT2 inhibitor to insulin therapy, Dr. Colburn recommends lowering a patient’s total daily insulin dose by 20-30% to prevent hypoglycemia –expert opinion.
Check a basic metabolic panel one week after initiation of an SGLT2i –expert opinion.
Dr. Colburn points out that lower limb amputations, euglycemic DKA and Fournier’s gangrene are infrequent adverse outcomes with the use of SGLT2 inhibitors and should not prevent most patients from deriving a therapeutic benefit –expert opinion.
Once weekly GLP1 agonists take about 5 half lives (5 weeks) to reach steady state. Dr. Colburn recommends lowering a patient’s total daily insulin dose by 20-30% to make room for these agents –expert opinion.
Dr. Colburn recommends starting at basal insulin of 0.2-0.3 units per kg body weight per day. Target a fasting glucose of 80-130 mg/dL and go up by 2 units every 3 days until goal –expert opinion. Add short acting insulin once basal insulin reaches more than 50 units per day. At that point the patient is adequately “basaled” –expert opinion.
Dr. Colburn recommends continuing metformin, GLP1 agonists and SGLT2 inhibitors in patients starting insulin therapy. They may serve as insulin sparing agents. Conversely, if adding a GLP1 agonist or SGLT2 inhibitor to insulin therapy, consider decreasing the current total daily dose of insulin by 20-30% to avoid hypoglycemia –expert opinion.
Kashlak Pearl: Dr. Colburn mentions the following rough calculation: A1C of 6% = average glucose of 126 mg/dL. Add 30 mg/dL for every 1% increase in A1C (e.g. 7% = average glucose 156 mg/dL and so forth).
Dr. Colburn notes that glycemic control in type 2 diabetes (T2DM) is probably a minor factor in preventing macrovascular disease (strokes and heart attacks) compared to control of lipids, hypertension and improved lifestyle factors. The discordance between the observed benefits of strict glycemic control and guideline recommendations for strict A1C targets has been pointed out by some prominent endocrinologists —Rodriguez-Gutierrez R, Montori V 2016. See previous Curbsiders’ episode for more details –#96 Diabetes, a1c targets and acp guidelines controversy.
Microvascular complications might be prevented by strict glycemic control (A1C <7%), but the data is based on surrogate markers (e.g. laser photocoagulation and albuminuria), NOT hard endpoints (e.g. renal failure, blindness, painful neuropathy) —Rodriguez-Gutierrez R, Montori V 2016.
The 2018 ACP Guidance Statement on A1C Targets for Glycemic Control in T2DM recommends an A1C of 7-8% for most patients with T2DM. The VA/DoD guidelines from 2017 (co authored by Dr. Colburn) share a similar target –see table below (Conlin PR, Colburn J et al 2017).
Consider a CGM for patients with T1DM or patients with T2DM on intensive insulin therapy. For most patients who need more intense monitoring, Dr. Colburn recommends checking glucose four times daily in the week before an office visit to get a sense of glucose control. Check fasting glucose (used to dose long acting insulins), before lunch, before dinner and one postprandial glucose (2 hrs after any meal) –expert opinion.
The DIRECT trial showed promise for reversal of T2DM during a primary care-led weight-management programme (Lean 2019). That said, Dr. Colburn worries that some patients may have already lost too much beta cell function to benefit from intense lifestyle modifications (i.e. they’ve lost the ability to produce sufficient insulin). Such patients will likely still need conventional therapy.
Dr Colburn recommends this resource to assist in shared decision making – Diabetes Medication Choice | Mayo Clinic Shared Decision Making …
See Figure 4 https://clinical.diabetesjournals.org/content/37/1/11.figures-only
Kashlak Pearl: When adding an SGLT2 inhibitor to insulin therapy, Dr. Colburn recommends lowering a patient’s total daily insulin dose by 20-30% to prevent hypoglycemia –expert opinion.
For more tips on how to use SGLT2 inhibitors —#51 Diabetes treatment in 2017: New meds, insulin, and cardiac risk reduction
SGLT2 inhibitors provide cardiovascular (Zelniker 2019) and renal protection (Sedu 2018, CREDENCE Trial 2019). But, they are not effective for patients with an eGFR under 30. Thus, they’re not recommended for use in CKD 4-5, mainly because of decreased effectiveness at lower GFRs. These agents are particularly good for preventing hospitalization for heart failure. Dr. Colburn attributes this to their ability to improve blood pressure by exerting a diuretic effect.
Dr. Colburn recommends stopping thiazide diuretics in patients initiating an SGLT2 inhibitor due to risk of AKI and hypovolemia. On the contrary, he often continues loop diuretics alongside SGLT2 inhibitors, especially if these patients are euvolemic or hypervolemic.
Kashlak Pearl: Check a basic metabolic panel one week after initiation of an SGLT2i –expert opinion.
Kashlak Pearl: Dr. Colburn points out that lower limb amputations, euglycemic DKA and Fournier’s gangrene are infrequent adverse outcomes and should not prevent most patients from deriving a therapeutic benefit –expert opinion.
SGLT2 inhibitors have a clear association with fungal infections of the genitals (vaginal candidiasis in women and balanitis in men) —Johnnson 2013.
Lower limb amputations were increased by two fold in patients taking SGLT2 inhibitors in a study of registry data (Ueda 2018). BUT, a recent pooled meta-analysis of randomized controlled trials found only a small increased risk of amputations (Donnan 2019). Many clinicians recommend avoiding these agents in patients with peripheral vascular disease or history of previous amputations until we have more information…but this remains expert opinion.
The FDA recently issued a warning about the association of SGLT2i with Fournier’s gangrene (Bersoff-Matcha 2019). Dr. Colburn points out that this complication is a rare occurrence.
An oral version of semaglutide seems promising and probably has similar outcomes to injectable GLP1 agonists (Husain 2019).
GLP1 is an endogenous hormone that improves glucose-dependent insulin release from the pancreas, decreases inappropriate glucagon secretion and slows gastric emptying (Lexicomp).
The LEADER trial (Marso 2016) and others since showed a reduction in cardiovascular events among those with known (or at high risk) for CV disease. These drugs are associated with weight loss and drop A1C values by about 2%. They rarely cause hypoglycemia and the main side effect is nausea.
Kashlak Pearl: Once weekly GLP1 agonists take about 5 half lives (5 weeks) to reach steady state. Dr. Colburn recommends lowering a patient’s total daily insulin dose by 20-30% to make room for these agents –expert opinion.
For more tips on how to use GLP1 agonists —#51 Diabetes treatment in 2017: New meds, insulin, and cardiac risk reduction
Dr. Colburn points out there is no clear benefit of any specific insulin formulation over others for patients with type 2 diabetes (e.g. glargine vs degludec OR aspart vs lispro).
Kashlak Pearl: Dr. Colburn recommends starting at basal insulin of 0.2-0.3 units per kg body weight per day. Target a fasting glucose of 80-130 mg/dL and go up by 2 units every 3 days until goal –expert opinion. Add short acting insulin once basal insulin reaches more than 50 units per day. At that point the patient is adequately “basaled” –expert opinion.
Kashlak Pearl: Dr. Colburn recommends continuing metformin, GLP1 agonists and SGLT2 inhibitors in patients starting insulin therapy. They may serve as insulin sparing agents. Conversely, if adding a GLP1 agonist or SGLT2 inhibitor to insulin therapy, consider decreasing the current total daily dose of insulin by 20-30% to avoid hypoglycemia –expert opinion.
Listeners will explain the pitfalls of hemoglobin A1C testing and targets; choose oral and injectable agents to manage type 2 diabetes (T2DM); and counsel patients about the risks and benefits of various treatment options.
After listening to this episode listeners will…
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Colburn J, Brigham SK, Williams PN, Watto MF. “#168 Diabetes Update with Jeff Colburn MD”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list. August 26, 2019.
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Comments
Greetings, what methodology was used for Hgb A1C testing that yielded the 0.5% variability?