Dental Diabetes Lecture_Dr. Alexanian PDF

Diabetes Overview Sara Alexanian MD Department of Endocrinology, Diabetes and Nutrition Boston Medical Center Overview ◼ ◼ ◼ ◼ ◼ Basics of insulin physiology, glucose homeostasis Types of diabetes, pathophysiology Complications of diabetes, acute and chronic Treatment of diabetes Issues in dent...

Diabetes Overview Sara Alexanian MD Department of Endocrinology, Diabetes and Nutrition Boston Medical Center Overview ◼ ◼ ◼ ◼ ◼ Basics of insulin physiology, glucose homeostasis Types of diabetes, pathophysiology Complications of diabetes, acute and chronic Treatment of diabetes Issues in dental care and diabetes The Basics insulin Glucose 60-120 mg/dL glucagon Fuel and Metabolism ◼ ◼ ◼ ◼ Glucose is the major source of energy in the body Glucose is absorbed in the small intestine, travels thru the bloodstream, and for many tissues requires insulin to enter into cells. Glucose is also released from the liver and kidneys. Protein and fat can also be broken down for fuel (fat becomes ketone bodies) Insulin is a “fed state” hormone Normal pancreatic function Insulin ◼ ◼ ◼ Manufactured in multistep process in the pancreatic beta cell. Released in 2 phases when glucose levels rise Carbs are the most effective stimulators of insulin release Glucagon ◼ ◼ Secreted from pancreatic alpha cells Acts on the liver to break down glycogen and increase gluconeogenesis Normal physiology: Insulin Promotes glucose storage INSULIN Glucose and amino acid transport Store triglycerides in fat cells, inhibits the breakdown of fat into fatty acids Incretin Hormones GLP-1 ▪ ▪ ▪ ▪ ▪ ▪ Released from L cells in ileum and colon1,2 Stimulates insulin response from beta cells in a glucose-dependent manner1 Inhibits gastric emptying1,2 Reduces food intake and body weight2 Inhibits glucagon secretion from alpha cells in a glucose-dependent manner1 Levels are low in type 2 DM3 GIP ▪ ▪ ▪ ▪ ▪ ▪ Released from K cells in duodenum1,2 Stimulates insulin response from beta cells in a glucose-dependent manner1 Minimal effects on gastric emptying 2 Has no significant effects on satiety or body weight2 Does not inhibit glucagon secretion from alpha cells1,2 Levels normal or high in type 2 DM3 1. Meier JJ et al. Best Pract Res Clin Endocrinol Metab. 2004;18:587–606. 2. Drucker DJ. Diabetes Care. 2003;26:2929 -2940. 3.Barnett AH. Clin Endocrinolgy. 2009;70:343-53. Incretins and Glucose Homeostasis Active GLP-1, GIP DPP-4* enzyme Inactive GLP-1, GIP Insulin from Beta cells Increase glucose uptake in muscles Lower BG Glucagon from a-cells (GLP-1) Decrease glucose production in liver *DPP-4 = dipeptidyl-peptidase 4 1. Kieffer TJ, Habener JF. Endocr Rev. 1999;20:876–913. 2. Ahrén B. Curr Diab Rep. 2003;2:365–372. 3. Drucker DJ. Diabetes Care. 2003;26:2929–2940. 4. Holst JJ. Diabetes Metab Res Rev. 2002;18:430–441. What Happens in Diabetes? ◼ ◼ Diabetes is not a single disorder. Occurs when glucose levels are elevated due to insulin deficiency, impaired insulin action in the setting of relative insulin insufficiency, or both. Type 1 Diabetes ◼ ◼ ◼ ◼ Results from immune-mediated destruction of the islet beta cell. Progresses over months to years, the individual is asymptomatic. About 7% of the population with diabetes. “absolute” insulin deficiency Type 2 Diabetes ◼ ◼ Characterized by insulin resistance in the liver, muscle and fat. “Relative” lack of insulin to control glucose levels. Progression of Type 2 Diabetes Genes Obesity, beta-cell mass, Insulin resistance Environment Inactivity, high-calorie diet Insulin resistance and hyperinsulinemia Beta-cell compensation Beta-cell decompensation: Prediabetes -> post-meal; hyperglycemia Type 2 Diabetes Decreased beta-cell mass Fasting hyperglycemia Low insulin levels elevated glucagon levels Other types of Diabetes ◼ ◼ ◼ ◼ ◼ ◼ Gestational diabetes Genetic defects of beta-cell function (MODY) Genetic defects in insulin action Endocrinopathies Drug or chemical induced Genetic syndromes Diagnosis ◼ ◼ ◼ Measure fasting serum glucose Measure post-carbohydrate serum glucose Measure 3 month average of serum glucose (hemoglobin A1c) Hemoglobin A1c Complications of Diabetes ◼ ◼ ◼ Acute complications Microvascular complications Macrovascular complications Diabetic Ketoacidosis (DKA) ◼ ◼ ◼ Acute event resulting from an acute insulin deficiency. More often associated with type 1 diabetes, may be the initial diagnostic event. In patients with known diabetes, generally preventable. Diabetic Ketoacidosis (DKA) ◼ ◼ Precipitating events: illness, infection, omission of insulin, medications, physiologic stress, substance abuse. Cause: insulin deficiency, increased counterregulatory hormones, dehydration. Normal physiology: Insulin Promotes glucose storage INSULIN Glucose and amino acid transport Store triglycerides in fat cells, inhibits the breakdown of fat into fatty acids Normal physiology: Counter-regulatory hormones (glucagon, cortisol, GH, epinephrine) Fat breakdown Glucose output Elevated glucose Fatty acids INSULIN Glucose cannot enter cell Diabetic Ketoacidosis (DKA) ◼ ◼ ◼ ◼ Clinical presentation: increased thirst, increased urination, vomiting, abdominal pain, weakness. Diagnosis: hyperglycemia, ketones, acidosis. Treatment: hospital admission (moderate to severe), insulin administration, fluids, treatment of precipitating event. Outcomes: mortality <5%. Hyperglycemic Hyperosmolar Syndrome (HHS) ◼ ◼ ◼ Acute hyperglycemia in the presence of some insulin, which prevents ketosis. More often seen in elderly type 2 diabetes, but can be seen in patients with type 1 diabetes. Can be precipitated by illness, infection, medications. Develops over days to weeks. Hyperglycemic Hyperosmolar Syndrome (HHS) ◼ ◼ ◼ ◼ Clinical presentation: increased thirst and urination, confusion, lethargy, coma. Findings: severe dehydration, severe hyperglycemia (>600 mg/dL), hyperosmolarity, small ketones. Treatment: medical emergency, ICU admission for fluids and insulin, treatment of underlying cause. Mortality: 5-20%. Microvascular Complications ◼ ◼ ◼ ◼ Development of these complications are directly related to diabetes and blood pressure control. Retinopathy Neuropathy Nephropathy Cotton wool spots Hemorrhages Neuropathy ◼ ◼ ◼ ◼ Cause: sorbitol, AGEs, oxidative stress, disruption of metabolic pathways. Most common: symmetric distal sensorimotor polyneuropathy Autonomic neuropathy Neuropathies of thoracic and lumbar region, cranial nerves. Nephropathy ◼ ◼ ◼ Early phase: increase blood flow, asymptomatic Development of microalbuminura Late phase: larger amounts of protein excretion in the urine, progressive decline in renal filtration ability. Treatment ◼ ◼ ◼ ◼ Glucose and blood pressure control Retinopathy: Panretinal photocoagulation, medications Nephropathy: medications Neuropathy: foot care and medications Conventional vs Intensive Insulin Therapy Glycemic Responses in Two Trials DCCT Kumamoto Study 1444 type 1 patients 110 type 2 patients  Conventional therapy  Conventional therapy Intensive therapy Median 11 A1C 10 (%) Intensive therapy Mean 11 A1C 10 (%)  A1C ~2.1% 9 9 8 ADA action 8 7 ADA goal 7 ACE goal 6  A1C ~2.3% 6 Normal range 5 0 1 2 3 4 5 6 7 5 8 9 10 Years DCCT Research Group. N Engl J Med. 1993;329:977-986; Ohkubo Y et al. Diabetes Res Clin Pract. 1995;28:103-117 Normal range 0 1 2 3 Years 4 5 6 Intensive Therapy Reduces Risk of Retinopathy and Nephropathy DCCT Retinopathy Cumulative percent progressing60 Primary Prevention 50 -76% 40 P<0.001 Conventional therapy Intensive therapy 30 Primary Prevention 25 -34% 20 P<0.04 15 10 5 0 30 20 10 0 60 Secondary Intervention 50 -54% 40 30 50 40 P<0.001 30 20 20 10 10 0 0 0 1 2 3 4 5 6 7 8 Microalbuminuria 9 0 Years DCCT Research Group. N Engl J Med. 1993;329:977-986 Secondary Intervention -43% P=0.001 1 2 3 4 5 6 7 8 9 Intensive Insulin Therapy Microvascular Risk Reduction in Two Trials Complication Reduction in Risk With 2% Reduction of A1C Study Retinopathy DCCT 63% Kumamoto 69% Nephropathy 54%* 70%† Neuropathy 60% Significantly improved * Albuminuria >300 mg/24 hr † Worsening of albuminuria >300 mg/24 hr DCCT Research Group. N Engl J Med. 1993;329:977-986; Ohkubo Y et al. Diabetes Res Clin Pract. 1995;28:103-117 Macrovascular complications ◼ ◼ ◼ Coronary artery disease, peripheral vascular disease, stroke. Increase likelihood of 2-3x compared to general population. Effects of hyperglycemia per se are unclear, treatment focuses on aggressive therapy for blood pressure and cholesterol. Summary ◼ ◼ ◼ Normal glucose homeostasis involves insulin (which moves glucose into cells), glucagon (which brings glucose into the serum), as well as GLP-1 and GIP. Diabetes is a diverse disorder, defined by an excess of serum glucose caused by relative or absolute insulin deficiency. Treatment of diabetes is important to prevent both the acute and chronic complications of the disease. Treatments for Diabetes Goals of Treatment ◼ ◼ ◼ ◼ Alleviate symptoms of uncontrolled diabetes. Decrease the likelihood of microvascular complications. Minimize side effects to treatments, weight gain, hypoglycemia Targets: HA1c <6.5% or 7%. Targets need to be individualized for patients. Lifestyle ◼ ◼ ◼ ◼ Hypocaloric diet: improvements in glucose with weight loss of even 5-10 lbs. Increased activity. Medical nutrition therapy. Pros: cost-effective, other health benefits. Cons: large percentage regain weight. Sulfonylureas ◼ ◼ ◼ ◼ ◼ Available since 1954. Glipizide, Glyburide, Gliclazide, Glimeperide Mechanism: bind to SU receptor, stimulates insulin secretion. Pros: long history of use, cost, efficacy, daily dosing, outcomes measurements. Cons: weight gain, hypoglycemia, (CV effects, beta-cell decline?), caution with renal and liver dysfunction. Biguanides ◼ ◼ ◼ ◼ Metformin available since 1995. Mechanism: reduce hepatic glucose output. May also increase insulin sensitivity. Pros: weight loss, no hypoglycemia, metabolic improvements, outcome measurements, history of use. Cons: GI side-effects, renal insufficiency and lactic acidosis. GLP-1 mimetics ◼ ◼ ◼ ◼ Exenatide, released in 2005, liraglutide,, dulaglutide, lixisenatide, semaglutide. Mechanism: increase insulin secretion in a glucose-dependent manner, decrease glucagon, slow gastric emptying. Pros: weight loss, no hypoglycemia, ?beta-cell mass. CV benefits. Cons: cost, injection, nausea/vomiting, short use duration. ?pancreatitis, contraindicated with GFR <30 mL/min. DPP-4 Inhibitors ◼ ◼ ◼ ◼ ◼ Approved in US in 2006. Sitaglipton, saxaglipton, linagliptin Mechanism: inhibit DPP-4, increase post-prandial rise in GLP-1. Pros: weight-neutral, no hypoglycemia, use in end stage renal disease. Cons: efficacy, experience, cost, rare allergic reactions. SGLT-2 inhibitors ◼ ◼ ◼ ◼ ◼ Approved 2013 Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin Mechanism: lower glucose clearance in the kidney causing it to be wasted in the urine. Pros: weight loss, no hypoglycemia. CV benefit. Cons: genital infections, cost, no longterm safety data. Less commonly used medications ◼ ◼ ◼ ◼ ◼ ◼ ◼ ◼ nateglinide, rapeglinide (non-SU secretagogues) Mechanism: stimulate insulin secretion, short metabolic half-life. Amylin: Pramlintide, approved in US in 2005. Mechanism: slows gastric emptying, increases satiety, suppresses glucagon. Acarbose: Introduced in US in 1996. Mechanism: inhibits α-glucosidase in small intestine, delay carbohydrate absorption. Pioglitazone: thiazoleadinedione class Mechanism: improve insulin sensitivity Insulin Treatment ◼ ◼ Required for all patients with type 1 diabetes. Also indicated in insulin deficient diabetes, patients with longstanding or poorly controlled type 2 diabetes. Pharmacokinetics of insulin preparations Short acting Analog Insulin Effect Regular NPH Glargine Detemir 8 AM N 6 PM 10 PM 8 AM 6-23 “Basal-Bolus” therapy Consistent carbohydrate diet order Glargine ( ~ 50 % ) Humalog/Novolog ( ~ 50 % ) 8 12 5 9 Insulin Pump therapy ◼ ◼ Insulin is infused via a subcutaneous catheter. The pump delivers a basal rate, the patient delivers boluses of insulin with meals and for hyperglycemia. Things to know about insulin pumps ◼ ◼ ◼ ◼ ◼ They deliver a continuous amount of insulin 24 hours a day automatically The do NOT respond independently to the patients’ blood sugars* Patients must test their blood sugars and instruct the pump In patient with type 1 diabetes they should not be removed for longer than 1-2 hrs Patients may or may not also be using a separate device (continuous glucose monitor, CGM), to monitor BG. *limited exception: Medtronic 670g Dental Care and Diabetes caries Gingivitis Lichen planus Burning mouth syndrome xerostomia Tooth loss Angular cheilitis abscesses candidiasis Taste dysfunction Considerations in Dental practice ◼ ◼ ◼ ◼ Be alert for patients with symptoms of diabetes but without a diagnosis – polyuria, polydipsia, weight change – and refer to a physician. Hypoglycemia Hyperglycemia Other issues Intake and History ◼ ◼ ◼ ◼ ◼ Medications Usual and most recent glucose measurements Amount and type of insulin History and frequency of severe hypoglycemia Symptoms of uncontrolled diabetes Hypoglycemia ◼ ◼ ◼ Which medications cause hypoglycemia? Sulfonylureas Insulin meglitinides ◼ ◼ Adrenergic sxs: anxiety, hunger, palpitations, sweating tremors Neuroglycopenic symptoms: coma, confusion, irritability, dizziness, hunger, seizures, weakness 90 normal 70 Counterregulatory hormone release 60 Adrenergic symptoms 50 Neuroglycopenic symptoms 40 lethargy coma seizure 30 20 Hypoglycemia ◼ ◼ ◼ ◼ ◼ ◼ Protocols should be established in the office to treat hypoglycemia Conscious: 15 g of carbohydrate (4 oz fruit juice, ½ can soda, 3-4 glucose tabs) Unconscious: administer IV dextrose or IM glucagon. Repeat FS in 15 minutes Pt should eat a snack For procedures requiring sedation: check FS prior and every hour. General considerations ◼ ◼ ◼ ◼ Morning appointments tend to be best Patients generally should take usual medications and eat as usual Have a glucose source available Advise pt to inform staff if any symptoms of low glucose General Considerations ◼ ◼ For patients with well-controlled diabetes, dental procedures can generally be performed without special precautions. If patients are not going to be able to eat normally, adjustments may need to be made to medications or insulin, in consultation with the patients’ physician. Hyperglycemia ◼ ◼ ◼ ◼ Having well-controlled glucose levels is important for healing and to prevent infection. Uncontrolled diabetes is a pro-inflammatory state associated with impaired wound healing and abnormalities in coagulation. There are no standard guidelines for when procedures need to be postponed. In patients with chronically poor diabetes control, further discussion about risks and benefits with the pt and physician are appropriate. Dental Disease ◼ Oral complications may include: ◼ ◼ ◼ ◼ ◼ ◼ ◼ ◼ Infections (bacterial, viral, fungal) Poor wound healing Increased incidence and severity of caries Gingivitis Periodontal disease Xerostomia Abcesses Oral burning sensation Dental Disease ◼ ◼ Dental and periodontal disease is more common in patients with diabetes. Prevalence of diabetes is higher in patients with periodontal disease. Epidemiology of Periodontitis ◼ ◼ Review of 48 studies (cross-sectional and prospective) between 1960-2000: 44/48 studies supported DM as a risk factor for periodontitis*. Review of 17 cross-sectional studies between 2000-2007: 13/17 showed periodontitis more severe and more prevalent in pts with DM**. *Taylor GW. Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective. Ann Periodontal 2001;6(1):99-112. **Taylor GW, Borgnakke WS. Periodontal disease: associations with diabetes, glycemic control and complications. Oral Dis 2008:14(3):191-203. Periodontitis and Glycemic control ◼ ◼ ◼ ◼ NHANES III: relationship between severe periodontitis and HA1c. 4,343 adults age 45-90 years old. Multivariate modeling used to control for other RFs: OR for having periodontitis in adults with poorly controlled DM (A1c > 9%) 2.9. If DM and A1c <9%, OR 1.56. Tsai et al, Glycemic control of type 2 diabetes and severe periodontal disease I the US adult population. Community dent oral eipdemiol 2002:30(3):182-92. Mechanisms? ◼ ◼ Formation of AGEs: AGEs bind to a receptor on endothelial cells and monocytes, causes an increase in inflammatory markers. Enhanced apoptosis may also contribute to delayed wound healing. Treatment of periodontitis ◼ ◼ ◼ Some evidence that treatment of periodontitis may improve glycemic control. Most studies are crosssectional, small studies, variation of population and length of follow-up. One randomized trial of non-surgical management of periodontal disease on 257 pts with DM2 was stopped early due to failure to show any effect on A1c. 1 Further studies are warranted to understand the relationship and its effect on patient health. 1. Engebretson SP et al, The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabe tes and chronic periodontitis: a randomized clinical trial, JAMA 2013 Summary ◼ ◼ ◼ ◼ Treatment of type 1 diabetes relies on insulin therapy Treatment of type 2 diabetes include oral and injectable medications in addition to insulin. There is an association between diabetes and periodontitis, both which are inflammatory conditions. Be aware of the dental consequences of diabetes, and the risks of chronic hyperglycemia and acute hypoglycemia. Thanks! Questions?