*With the exception of programs from the ACCEL series, each of which qualifies for up to 4 Category 1 CME credits.
Audio-Digest Family Practice
Volume 61, Issue 02
January 14, 2013
Diabetes Management Sherry K. Sussman, MD
Diabetes and Eating Disorders Ovidio Bermudez, MD
The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.
Family Practice Program Info Accreditation InfoCultural & Linguistic Competency Resources
Update on Diabetes
The goal of this program is to improve management of diabetes. After hearing and assimilating this program, the clinician will be better able to:
1. Discuss risks and benefits of metformin, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 analogues.
2. Improve glucose levels between meals by selecting the appropriate form of insulin based on onset and duration.
3. Describe common methods of insulin manipulation by patients with eating disorder and type 1 diabetes (ED-DMT1).
4. Recognize risk factors for development of ED-DMT1.
5. Counsel patients with ED-DMT1 in a multidisciplinary setting to reach goal of self-management.
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Sussman is on the Speakers’ Bureaus for Abbott Laboratories, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, and sanofi-aventis US. Dr. Bermudez and the planning committee reported nothing to disclose.
Sherry K. Sussman, MD, Clinical Associate Professor of Medicine, State University of New York at Stony Brook, Smithtown, NY
Diagnosis of diabetes: fasting blood glucose (FBG) ≥126 mg/dL, 2-hr glucose >200 mg/dL, random glucose >200 mg/dL with signs and symptoms of diabetes, or hemoglobin A1c (HbA1c) ≥6.5%
Treatment of diabetes: cabergoline — not approved in United States; pioglitazone — thiazolidinedione; indicated for diabetes; pramlinitide — amylin analogue; amylin normally cosecreted with insulin; patients with type 2 diabetes, deficient in amylin; patients with type 1 diabetes do not secrete insulin or amylin; inhibits glucagon secretion (prevents secretion of glucose from liver), slows gastric emptying, promotes satiety, and reduces caloric intake; indicated for treatment of patients with type 2 diabetes who are on insulin and patients with type 1 diabetes; increased incidence of severe hypoglycemia when used in combination with insulin (usually occurs within first 3 hr of injection; patients must closely monitor glucose levels when starting medication); multiple injections may be difficult to manage for some patients; colesevelam — bile acid resin; used in patients with lipid abnormalities; found to lower glucose and HbA1c levels by ≈0.5%; approved by Food and Drug Administration (FDA) for lowering glucose and HbA1c in diabetics; bromocriptine (Cycloset, Parlodel) — indicated for diabetes; low dose found to lower glucose and HbA1c; thought to reset aberrant low morning hypothalamic dopaminergic activity; 0.8-mg pill taken with food within 2 hr of waking in morning; maximum of 6 pills/day; start with 1 pill, then titrate up; in clinical trials, most patients needed 3 to 4 pills/day for diabetes control
Metformin: generally does not cause hypoglycemia or weight gain; United Kingdom Prospective Diabetes Study (UKPDS) saw significant decline in myocardial infarction (MI) in overweight or obese patients on metformin (overall, MI trend slightly short of statistical significance); 10-yr follow-up study of intensive glucose control in patients with type 2 diabetes saw early loss in difference in glucose control with continued reduction in microvascular risk, and noted emergent risk reductions for MI and death from any cause; conclusions — continued benefit noted after metformin therapy in mildly overweight patients
Pioglitazone: Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) study did not show reduction in (nor increased risk for) MI, compared to placebo; pioglitazone associated with greater decrease in intima-media thickness, compared to glimepiride
Lactic acidosis and congestive heart failure (CHF): can occur in diabetic patients treated with metformin; study — looked at 47 patients with lactic acidosis; 43 had ≥1 risk factor for lactic acidosis; 64% had preexisting cardiac disease (18 had histories of CHF); bibasilar rales, shortness of breath, and leg edema suggestive of CHF; side effects of pioglitazone include increased fluid retention and CHF; according to UKPDS, neither sulfonylureas nor insulin therapy associated with increased cardiovascular (CV) mortality
Incretins: include dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogues; patients given oral load of glucose found to have greater insulin response than patients given intravenous load (incretin effect; diminished in type 2 diabetics); action of GLP-1 — GLP-1 secreted from L cells in intestine when food ingested; this stimulates glucose-dependent insulin secretion, suppresses hepatic glucose output by decreasing secretion of glucagon, slows gastric emptying, and leads to reduced food intake; many patients lose weight when using GLP-1 analogues (no weight loss associated with use of DPP-4 inhibitors); action of DPP-4 inhibitors — inhibit enzyme that breaks down incretins (GLP-1 and gastric inhibitory polypeptide), leading to continued enhancement of insulin secretion and suppression of glucagon; glucose-dependent (ie, infusing GLP-1 continuously, glucose levels drop, and insulin levels increase; after time, insulin secretion decreases)
DPP-4 inhibitors: sitagliptin (Januvia) — once-daily dosing; available in combination with metformin; 2 dose adjustments for renal insufficiency; saxagliptin (Onglyza) — once-daily dosing; available in combination pill with metformin; 1 dose adjustment for renal insufficiency; linagliptin (Tradgenta) — once-daily dosing; no dose adjustment for renal insufficiency
GLP-1 analogues: exenatide (Byetta) — twice-daily dosing; liraglutide (Victoza) — once-daily dosing; black box warning (high doses used in mice resulted in higher incidence of medullary thyroid cancer); side effects — nausea (tends to abate with multiple doses; persists and intolerable in some patients); weight loss; small risk for pancreatitis; exenatide extended-release (Bydureon) — once-weekly dosing; patients must be trained on how to use small syringe; black box warning about increased risk for medullary thyroid cancer seen in rats
Summary of insulins: insulin lispro, aspart, or glulisine — rapid acting; onset in 5 to 15 min; last 1 to 2 hr; human regular insulin — onset in 30 to 60 min; lasts 2 to 4 hr; insulin isophane (NPH) and insulin zinc suspension (lente) — onset in 1 to 2 hr; last 4 to 8 hr; insulin glargine or detemir — can last up to 24 hr; basal-bolus concept — bolus insulin covers postprandial period; basal insulin provides overnight coverage and between meals in fasting state; ideal basal insulin — long-acting; peakless; provides continuous steady stream into blood; basal insulin requirements — 0.3 to 0.7 units/kg per day (≈50% of total daily insulin); can be affected by activity, stress, and menstrual cycle; premeal insulins — rapid acting; improve postprandial glucose levels; when insufficient, glucose level increases between meals
Diabetes and Eating Disorders
Ovidio Bermudez, MD, Medical Director, Child and Adolescent Services, Eating Recovery Center, Denver, CO
Introduction: obesity not eating disorder (ED) or mental illness; according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV), EDs encompass anorexia nervosa (AN), bulimia nervosa, and ED not otherwise specified (eg, binge-eating disorder); according to proposed criteria of EDs for DSM-5, childhood eating pathologies (eg, extreme picky eating, emotional food avoidance) fold into EDs; bulimia nervosa described in 1979 as malignant variant of AN and recognized in DSM in 1980; overweight and obesity most common chronic diseases in adolescent girls (AN third most common); literature suggests relation between EDs and diabetes
New presentations of ED modalities: anorexia athletica — individuals manage weight based on obsession with athleticism; bulimic multi-impulsive syndrome — bulimia as part of spectrum of mood dysregulation and intolerance of distress, leading to reactivity and impulsivity in many areas of life; orthorexia — drive to eat high-quality foods, leading to impairment in health; manorexia — applies specifically to men; pregorexia — EDs that develop or significantly exacerbate during pregnancy; drunkorexia — individuals restrict calories from food in order to drink them in form of alcohol beverages in evening; other — muscle dysphoria; diabulimia; insulin manipulation — for purpose of weight management; not mentioned in DSM-IV; diabetic patients with bulimia may choose to neglect their insulin treatments
EDs and diabetes: 2008 consensus statement — concluded that type 1 diabetes should be considered risk factor for development of ED; EDs that fit criteria for binge-eating disorder should be considered risk factor for type 2 diabetes; poor regulation of glucose in diabetic patients has significant consequences (some reversible); diabetic patients in late teenage years or at early college age may be intentionally manipulating insulin for purpose of weight management
ED in patients with type 1 diabetes (ED-DMT1): intentional omission of prescribed insulin (by, eg, strategically decreasing, delaying, or completely omitting) for purpose of inducing hyperglycemia and rapidly losing calories in urine in form of glucose, and thus weight loss or avoidance of weight gain
Insulin manipulation: “disabling” of insulin — through, eg, heat exposure or short microwaving; impairing absorption — injecting insulin into sites of atrophy or indurations; “leaking the shots” (ie, patients appear to be injecting insulin, but know that significant portion of dose nonfunctional); pump manipulation — cutting off basal delivery temporarily; using basal insulin but not covering for carbohydrate intake; underdosing for binges — dosing for regular eating, but skipping doses when patients feel as though they overate
Manipulation of glucose readings: using control solution to obtain “perfect” readings; using alcohol on test strips; diluting blood with water; substituting with orange juice instead of blood
Risk factors associated with diabetes care: dietary restraint (eg, meal planning and carbohydrate counting); psychosocial implications of living with diet; learning deregulated eating based on external cues (eg, diabetics eat when they have to); exercise as glucose control aid; availability of deliberate insulin omission; depression (incidence in diabetics twice as high as in general population); every patient with type 1 diabetes should be considered at risk for eating-related pathology
Predictive factors for ED-DMT1: clinical — disordered eating behaviors; excessive exercise; insulin reduction or omission; early microvascular disease; multiple episodes of diabetic ketoacidosis (DKA) otherwise unexplained; poor glycemic control; recurrent hypoglycemia (leads to bingeing); demographic and psychosocial — lower socioeconomic status; less cohesive family structure; higher sense of distress; drive for perfection; intense focus on numbers
Model for pathogenesis of ED-DMT1: treatment goals (eg, near normal glycemia, carbohydrate counting, portion control, dietary restraint) may lead to frustration with abnormal blood glucose levels and weight gain (especially in patients with perfectionism); patients may feel deprived by dietary restraints and fall into binge-eating cycles, resulting in weight gain (reinforces frustration); patients often develop symptoms of depression and negative feelings about weight and body shape; leads to hyperglycemia, elevated HbA1c, and intentional omission or manipulation of insulin for purpose of caloric purging (self-reinforcing; leads to worse glycemic control; results in weight loss)
Epidemiology: prevalence of ED-DMT in girls and women — for full-syndrome ED, 0% to 11%; for subthreshold (ie, patients do not completely meet criteria for AN or bulimia, but engage in intentional insulin manipulation, or ED not otherwise specified), 7% to 35%; findings from studies — EDs twice as common in teenage girls with type 1 diabetes, compared to nondiabetics; increased risk for disturbed eating behavior in girls with type 1 diabetes detected from preteen years; disturbed eating behavior reported by diabetic girls as young as 9 yr of age; deliberate insulin omission as method of purging in girls with type 1 diabetes becomes progressively more common during teenage and college years
Clinical presentation of intentional insulin manipulation: weight loss; poor diabetic control; elevated HbA1c in spite of good records; recurrent DKA; early appearance or rapid advancement of diabetic complications; study — followed 91 girls 12 to 18 yr of age with type 1 diabetes (mean duration 7 yr) for 4 yr; at baseline, 38% dieting, 45% binge eating, 14% omitting or manipulating insulin, and 8% self-inducing vomiting; after 4 yr, 50% dieting, 50% binge eating, and 33% manipulating insulin; patients discover that omitting insulin more effective for weight loss than self-induced vomiting
Diabetic morbidity and mortality: poor diabetic control leads to rapid acceleration of diabetic complications; study found disturbed eating at baseline led to 3 times rate of retinopathy after 4 yr (more predictive of retinopathy than duration of diabetes alone); 10-yr Scandinavian registry retrospective study saw 2.2 deaths per 1000 person-years in type 1 diabetes alone, (7.3 deaths per 1000 person-years for AN alone; 34.8 deaths per 1000 person-years for dual diagnosis of type 1 diabetes and AN)
Management: all patients with type 1 diabetes diagnosed with ED should be considered for in-hospital stabilization (medical or ED inpatient facility) due to risk for high morbidity and mortality; assessment — look for complications of diabetes and ED; look for signs of depression or suicide risk; assess readiness for change; consider risk of travel to facility; EDs difficult to control in unprepared medical settings; formalize diagnosis of ED with diabetes as associated dual diagnosis; “assume then resume” approach to diabetic care — 1) all care assumed by staff; 2) joint care by staff and patient; 3) care resumed by patient as he or she gradually weans off supervision and demonstrates capacity to self-manage; initially aim for modest glucose control, then gradually aim for tighter control; institute predictable and reliable protocols for blood glucose testing and insulin administration
Important considerations: structure and predictability in management important; goal to turn control over to patient (ie, self-care); need for multidisciplinary expert team and for retraining in diabetes care; controversy about diabetic exchanges vs actual grams of carbohydrates (exchanges used as way of teaching plating and balancing intake); help patients recognize relativity of hypoglycemia; address tendency to overcontrol diabetes, focusing on obsessive sensitivity to hyper- or hypoglycemia; prepare patients for weight gain with improved diabetic control; issues of group dynamics (eg, comparison, competition, contagion, self-alienation); do not forbid foods or have special foods; start with using equipment (eg, insulin pumps) that belongs to facility rather than to patient; patients who have manipulated insulin pumps should come off pumps; discuss benefits of exercise; improvement in HbA1c more rapid than expected; be mindful that patients returning to antirecovery environment (eg, exposure to availability of fast food and media)
Future directions: fields of diabetology and EDs must not only inform each other, but work together; prevention efforts must begin with all professionals who interact with patients with type 1 diabetes and maintaining high index of suspicion for development of ED; early and ongoing screening of all type 1 diabetics for ED-related pathology; research in evidence-based approaches to modify diabetes education and management approaches for girls and women with increased risk for ED
Conclusion: EDs more common in patients with type 1 diabetes than in general population; conditions significantly affect physical and emotional well-being of patients with diabetes and associated with impaired metabolic control, high risk for medical complications, and high mortality rates; clinical care should be offered only in settings with expertise to address clinical complexity of dual diagnosis
Dr. Sussman spoke in Stony Brook, NY, at Maurice Goldenhar 38th Annual Family Medicine Update 2012, presented March 21-23, 2012, by Department of Family Medicine at Stony Brook School of Medicine. Please visit http://medicine.stonybrookmedicine.edu/cme/courses for information about course offerings from this sponsor. Dr. Bermudez was recorded in North Charleston, SC, at the 17th Annual Diabetes Fall Symposium for Primary Health Care Professionals, presented September 15-16, 2011, by Medical University of South Carolina and the Diabetes Initiative of South Carolina. Visit http://cme.musc.edu for information about upcoming conferences from the Medical University of South Carolina. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
Ali S, Fonseca V: Saxagliptin overview: special focus on safety and adverse effects. Expert Opin Drug Saf. 2012 Nov 9 [Epub ahead of print]; Chang CT et al: Metformin-associated lactic acidosis: case reports and literature review. J Nephrol. 2002 Jul-Aug;15(4):398-402; Colton P et al: Disturbed eating behavior and eating disorders in preteen and early teenage girls with type 1 diabetes: a case-controlled study. Diabetes Care. 2004 Jul;27(7):1654-9; Fang J et al: Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes. AAPS J. 2012 Oct 2 [Epub ahead of print]; Gallwitz B: Glucagon-like peptide-1 analogues for Type 2 diabetes mellitus: current and emerging agents. Drugs. 2011 Sep 10;71(13):1675-88; Goebel-Fabbri AE et al: Identification and treatment of eating disorders in women with type 1 diabetes mellitus. Treat Endocrinol. 2002;1(3):155-62; Jones JM et al: Eating disorders in adolescent females with and without type 1 diabetes: cross sectional study. BMJ. 2000 Jun 10;320(7249):1563-6; Nielsen S et al: Mortality in concurrent type 1 diabetes and anorexia nervosa. Diabetes Care. 2002 Feb;25(2):309-12; Olansky L: Q: Do incretin drugs for type 2 diabetes increase the risk of acute pancreatitis? Cleve Clin J Med. 2010 Aug;77(8):503-5; Park H et al: Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta-analysis. Ann Pharmacother. 2012 Nov;46(11):1453-69; Peveler RC et al: Eating disorders in adolescents with IDDM. A controlled study. Diabetes Care. 1992 Oct;15(10):1356-60; Rodin G et al: Eating disorders in young women with type 1 diabetes mellitus. J Psychosom Res. 2002 Oct;53(4):943-9; Rydall AC et al: Disordered eating behavior and microvascular complications in young women with insulin-dependent diabetes mellitus. N Engl J Med. 1997 Jun 26;336(26):1849-54; Scheen AJ: Outcomes and lessons from the PROactive study. Diabetes Res Clin Pract. 2012 Sep 25 [Epub ahead of print]; Viner R, Booy R: Epidemiology of health and illness. BMJ. 2005 Feb 19;330(7488):411-4; Walker JD et al: Mortality in concurrent type 1 diabetes and anorexia nervosa. Diabetes Care. 2002 Sep;25(9):1664-5; Wilding JP, Hardy K: Glucagon-like peptide-1 analogues for type 2 diabetes. BMJ. 2011 Feb 16;342:d410; Young V et al: Eating problems in adolescents with Type 1 diabetes: a systematic review with meta-analysis. Diabet Med. 2012 Aug 22 [Epub ahead of print].
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