Diabetes Mellitus
Diabetes MellitusIin Novita Nurhidayati MahmudaInternal Medicine Faculty of medicine Muhammadiyah University of Surakarta
1Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both.
The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
The effects of diabetes mellitus include longterm damage, dysfunction and failure of various organs.What is diabetes?
2Diabetes mellitus may present with characteristic symptoms such as thirst, polyuria, blurring of vision, and weight loss.
In its most severe forms, ketoacidosis or a nonketotic hyperosmolar state may develop and lead to stupor, coma and, in absence of effective treatment, death.
Often symptoms are not severe, or may be absent, and consequently hyperglycaemia sufficient to cause pathological and functional changes may be present for a long time before the diagnosis is made.Diabetes 3The longterm effects of diabetes mellitus include progressive development of the specific complications of retinopathy with potential blindness, nephropathy that may lead to renal failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints, and features of autonomic dysfunction, including sexual dysfunction.
People with diabetes are at increased risk of cardiovascular, peripheral vascular and cerebrovascular disease.Diabetes Long-term Effects4The development of diabetes is projected to reach pandemic proportions over the next10-20 years.
International Diabetes Federation (IDF) data indicate that by the year 2025, the number of people affected will reach 333 million 90% of these people will have Type 2 diabetes.
In most Western societies, the overall prevalence has reached 4-6%, and is as high as 10-12% among 60-70-year-old people.
The annual health costs caused by diabetes and its complications account for around 6-12% of all health-care expenditure.Burden of Diabetes 5Type 1 Diabetes Mellitus Type 2 Diabetes MellitusGestational DiabetesOther types:LADA (Latent Autoimun Diabetes of Adult )MODY (maturity-onset diabetes of youth)Secondary Diabetes Mellitus
Types of Diabetes
6Was previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. Type 1 diabetes develops when the bodys immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin that regulates blood glucose. This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. Type 1 diabetes may account for 5% to 10% of all diagnosed cases of diabetes. Risk factors for type 1 diabetes may include autoimmune, genetic, and environmental factors.
Type 1 diabetes 7Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. Type 2 diabetes may account for about 90% to 95% of all diagnosed cases of diabetes. It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce insulin. Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Native Hawaiians or Other Pacific Islanders are at particularly high risk for type 2 diabetes. Type 2 diabetes is increasingly being diagnosed in children and adolescents.Type 2 diabetes 8
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10A form of glucose intolerance that is diagnosed in some women during pregnancy. Gestational diabetes occurs more frequently among African Americans, Hispanic/Latino Americans, and American Indians. It is also more common among obese women and women with a family history of diabetes. During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant. After pregnancy, 5% to 10% of women with gestational diabetes are found to have type 2 diabetes. Women who have had gestational diabetes have a 20% to 50% chance of developing diabetes in the next 5-10 years.Gestational diabetes 11Other specific types of diabetes result from specific genetic conditions (such as maturity-onset diabetes of youth), surgery, drugs, malnutrition, infections, and other illnesses.
Such types of diabetes may account for 1% to 5% of all diagnosed cases of diabetes. Other types of DM12Latent Autoimmune Diabetes in Adults (LADA) is a form of autoimmune (type1 diabetes) which is diagnosed in individuals who are older than the usual age of onset of type 1 diabetes. Alternate terms that have been used for "LADA" include Late-onset Autoimmune Diabetes of Adulthood, "Slow Onset Type 1" diabetes, and sometimes also "Type 1.5 Often, patients with LADA are mistakenly thought to have type2 diabetes, based on their age at the time of diagnosis.
LADAAutoimmune (type1 diabetes) type2 diabetes13LADA (cont.)
14About 80% of adults apparently with recently diagnosed Type 2 diabetes but with GAD auto-antibodies (i.e. LADA) progress to insulin requirement within 6 years.
The potential value of identifying this group at high risk of progression to insulin dependence includes:the avoidance of using metformin treatmentthe early introduction of insulin therapyLADA (cont.)15MODY Maturity Onset Diabetes of the Young
MODY is a monogenic form of diabetes with an autosomal dominant mode of inheritance:Mutations in any one of several transcription factors or in the enzyme glucokinase lead to insufficient insulin release from pancreatic -cells, causing MODY.Different subtypes of MODY are identified based on the mutated gene.
Originally, diagnosis of MODY was based on presence of non-ketotic hyperglycemia in adolescents or young adults in conjunction with a family history of diabetes.
However, genetic testing has shown that MODY can occur at any age and that a family history of diabetes is not always obvious.MODY16MODY (cont.)
17Within MODY, the different subtypes can essentially be divided into 2 distinct groups: glucokinase MODY and transcription factor MODY, distinguished by characteristic phenotypic features and pattern on oral glucose tolerance testing.
Glucokinase MODY requires no treatment, while transcription factor MODY (i.e. Hepatocyte nuclear factor -1alpha) requires low-dose sulfonylurea therapy and PNDM (caused by Kir6.2 mutation) requires high-dose sulfonylurea therapy.MODY (cont.)18Secondary causes of Diabetes mellitus include:
Acromegaly, Cushing syndrome, Thyrotoxicosis, PheochromocytomaChronic pancreatitis, CancerDrug induced hyperglycemia:Atypical Antipsychotics - Alter receptor binding characteristics, leading to increased insulin resistance.Beta-blockers - Inhibit insulin secretion.Calcium Channel Blockers - Inhibits secretion of insulin by interfering with cytosolic calcium release.Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium channels.Naicin - They cause increased insulin resistance due to increased free fatty acid mobilization.Phenothiazines - Inhibit insulin secretion.Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause increased insulin resistance due to increased free fatty acid mobilization.
Secondary DM19Prediabetes is a term used to distinguish people who are at increased risk of developing diabetes. People with prediabetes have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Some people may have both IFG and IGT.
IFG is a condition in which the fasting blood sugar level is elevated (100 to 125 milligrams per decilitre or mg/dL) after an overnight fast but is not high enough to be classified as diabetes.
IGT is a condition in which the blood sugar level is elevated (140 to 199 mg/dL after a 2-hour oral glucose tolerance test), but is not high enough to be classified as diabetes.
Prediabetes: Impaired glucose tolerance and impaired fasting glucose
20Progression to diabetes among those with prediabetes is not inevitable. Studies suggest that weight loss and increased physical activity among people with prediabetes prevent or delay diabetes and may return blood glucose levels to normal.
People with prediabetes are already at increased risk for other adverse health outcomes such as heart disease and stroke.
Prediabetes: Impaired glucose tolerance and impaired fasting glucose (cont.)21Diagnosis of Diabetes Mellitus
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Values of Diagnosis of Diabetes Mellitus
25Principal Management in Type 2 Diabetes Mellitus*
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EDUCATION
1PHARMACOLOGIC TREATMENT
PHYSICAL ACTIVITYMEDICAL NUTRITION THERAPY* Konsensus Pengelolaan Diabetes Melitus di Indonesia, Perkeni 2011.Diet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.
Dietary treatment should aim at:ensuring weight controlproviding nutritional requirementsallowing good glycaemic control with blood glucose levels as close to normal as possiblecorrecting any associated blood lipid abnormalitiesA. Diet27The following principles are recommended as dietary guidelines for people with diabetes:
Dietary fat should provide 25-35% of total intake of calories but saturated fat intake should not exceed 10% of total energy. Cholesterol consumption should be restricted and limited to 300 mg or less daily.
Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable body weight). Requirements increase for children and during pregnancy. Protein should be derived from both animal and vegetable sources.
Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.
Excessive salt intake is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy.A. Diet (cont.)28Physical activity promotes weight reduction and improves insulin sensitivity, thus lowering blood glucose levels.
Together with dietary treatment, a programme of regular physical activity and exercise should be considered for each person. Such a programme must be tailored to the individuals health status and fitness.
People should, however, be educated about the potential risk of hypoglycaemia and how to avoid it.Exercise 29There are currently four classes of oral anti-diabetic agents:
i. Biguanidesii. Insulin Secretagogues Sulphonylureasiii. Insulin Secretagogues Non-sulphonylureas (Glinid) iv. -glucosidase inhibitorsv. Thiazolidinediones (TZDs)vi. DPP IV Inhibitor B. Oral Anti-Diabetic Agents
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T2DM Antihyperglycemic Therapy: General Recommendations
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]Moving from the top to the bottom of the figure, potential sequences of anti-hyperglycaemic therapy. In most patients, begin with lifestyle changes; metformin monotherapy is added at, or soon after, diagnosis (unless there are explicit contraindications).
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T2DM Antihyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]If the A1c target is not achieved after ~3 months, consider one of the 5 treatment options combined with metformin (dual combination): a sulfonylurea, TZD, DPP-4 inhibitor, GLP-1 receptor agonist or basal insulin. Note that the order in the chart is determined by historical introduction andr oute of administration and is not meant to denote any specific preference. Choice is based on patient and drug characteristics, with the over-riding goal of improving glycemic control while minimizing side effects. Shared decision-making with the patient may help in the selection of therapeutic options. Rapid-acting secretagogues (meglitinides) may be used in place of sulfonylureas. Consider in patients with irregular meal schedules or who develop late postprandialhypoglycemia on sulfonylureas. Other drugs not shown (-glucosidase inhibitors, colesevelam, dopamine agonists, pramlintide) may be used where available in selected patients but have modest efficacy and/or limiting side effects.
In patients intolerant of, or with contraindications for, metformin, select initial drug from other classes depicted, and proceed accordingly.
Consider starting with 2-drug combinations in patients with very high HbA1c (e.g. 9%).
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T2DM Antihyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]Further progression to 3-drug combinations are reasonable if 2-drug combinations do not achieve target. If metformin contraindicated or not tolerated, while published trials are generally lacking, it is reasonable to consider 3-drug combinations other than metformin.
Insulin is likely to be more effective than most other agents as a third-line therapy, especially when HbA1c is very high (e.g. 9.0%). The therapeutic regimen should include some basal insulin before moving to more complex insulin strategies (see Fig. 3)
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Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]Ultimately, more intensive insulin regimens may be required (see Figure 3.)
Dashed arrow line on the left-hand side of the figure denotes the option of a more rapid progression from a 2-drug combination directly to multiple daily insulin doses, in those patients with severe hyperglycaemia (e.g. HbA1c 10.0-12.0%).
Consider beginning with insulin if patient presents with severe hyperglycemia (300-350 mg/dl [16.7-19.4 mmol/l]; HbA1c 10.0-12.0%) with or without catabolic features (weight loss, ketosis, etc).
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As first line therapy:
Obese type 2 patients, consider use of metformin, acarbose or TZD.
Non-obese type 2 patients, consider the use of metformin or insulin secretagogues
Metformin is the drug of choice in overweight/obese patients. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin.
If monotherapy fails, a combination of TZDs, acarbose and metformin is recommended. If targets are still not achieved, insulin secretagogues may be addedB.1 Oral Agent Monotherapy (cont.)37Combination oral agents is indicated in:
Newly diagnosed symptomatic patients with HbA1c >10
Patients who are not reaching targets after 3 months on monotherapyB.2 Combination Oral Agents
38If targets have not been reached after optimal dose of combination therapy for 3 months, consider adding intermediate-acting/long-acting insulin (BIDS).
Combination of insulin+ oral anti-diabetic agents (BIDS) has been shown to improve glycaemic control in those not achieving target despite maximal combination oral anti-diabetic agents.
Combining insulin and the following oral anti-diabetic agents has been shown to be effective in people with type 2 diabetes:Biguanide (metformin)Insulin secretagogues (sulphonylureas)Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an approved indication)-glucosidase inhibitor (acarbose)
Insulin dose can be increased until target FPG is achieved.B.3 Combination Oral Agents and Insulin
39Oral Hypoglycaemic Medications
40In elderly non-obese patients, short acting insulin secretagogues can be started but long acting Sulphonylureas are to be avoided. Renal function should be monitored.
Oral anti-diabetic agent s are not recommended for diabetes in pregnancy
Oral anti-diabetic agents are usually not the first line therapy in diabetes diagnosed during stress, such as infections. Insulin therapy is recommended for both the above
Targets for control are applicable for all age groups. However, in patients with co-morbidities, targets are individualized
When indicated, start with a minimal dose of oral anti-diabetic agent, while reemphasizing diet and physical activity. An appropriate duration of time (2-16 weeks depending on agents used) between increments should be given to allow achievement of steady state blood glucose controlGeneral Guidelines for Use of Oral Anti-Diabetic Agent inDiabetes
41Type 1 diabetesUncontrolled type 2 diabetes.Gestasional diabetesLiver/renal insufficiency.Acute infection (celulitis, gangren), TBC, stroke/AMI.KAD/HHSMajor surgeryUnder weight, MRDMGraves diseaseCancerCorticosteroid treatment
Terapi insulin The majority of patients will require more than one daily injection if good glycaemic control is to be achieved. However, a once-daily injection of an intermediate acting preparation may be effectively used in some patients.
Twice-daily mixtures of short- and intermediate-acting insulin is a commonly used regimen.
In some cases, a mixture of short- and intermediate-acting insulin may be given in the morning. Further doses of short-acting insulin are given before lunch and the evening meal and an evening dose of intermediate-acting insulin is given at bedtime.
Other regimens based on the same principles may be used.
A regimen of multiple injections of short-acting insulin before the main meals, with an appropriate dose of an intermediate-acting insulin given at bedtime, may be used, particularly when strict glycaemic control is mandatory.Insulin regimens
43Overview of Insulin and Action
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45Patients should be educated to practice self-care. This allows the patient to assume responsibility and control of his / her own diabetes management. Self-care should include:
Blood glucose monitoringBody weight monitoringFoot-carePersonal hygieneHealthy lifestyle/diet or physical activityIdentify targets for controlStopping smoking
Self-Care
46 Komplikasi DiabetesKomplikasi akut Komplikasi kronis mikroangiopathy makroangiopathy hipoglikemi Keto-asidosis diabetik Koma hiperglikemi hiperosmoler non-ketotik hiperglikemi 47
Diabetic RetinopathyLeading causeof blindnessin adults1,2 Diabetic NephropathyLeading cause of end-stage renal disease3,4CardiovascularDiseaseStroke2- to 4-fold increase in cardiovascular mortality and stroke5DiabeticNeuropathy8/10 individuals with diabetes die from CV events6
1UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:111. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99S102. 3The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:309317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94S98. 5Kannel WB, et al. Am Heart J 1990; 120:672676.6Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences. 7Kings Fund. Counting the cost. The real impact of non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78S79.Peripheral Arterial DiseaseMicroangiopathyMacroangiopathy48Serious microvascular and macrovascular complications of type 2 diabetes have a devastating effect on quality of life and impose a heavy burden on healthcare systems.Diabetic retinopathy: present in 21% of people at the time type 2 diabetes is diagnosed,1 diabetic retinopathy is the leading cause of new blindness among adults aged 2074 years.2 Diabetic nephropathy: present in 18% of people diagnosed with diabetes;3 diabetes is a leading cause of end-stage renal disease.4Stroke: diabetes is associated with a 2- to 4-fold increase in cardiovascular mortality and stroke.5 Cardiovascular disease: 75% of individuals with type 2 diabetes die from cardiovascular causes.6Diabetic neuropathy: present in 12% of people at diagnosis,1 diabetic neuropathy affects approximately 70% of people with diabetes7 and is a leading cause of non-traumatic lower extremity amputations.8In the UKPDS, 50% of individuals with diabetes already had complications at diagnosis.9 Early detection and treatment of diabetes is essential in order to reduce the impact of its serious complications. 1UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:111. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99S102. 3The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:309317.4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94S98. 5Kannel WB, et al. Am Heart J 1990; 120:672676. 6Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences.7Kings Fund. Counting the cost. The real impact of non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78S79.9UKPDS Group. Diabetologia 1991; 34:877890. Chronic complications treatment and managementGlycemic controlBlood pressure controlLipid controlOthers: healthy lifestyle and diet schedulingSome distinctive methods:Retinopathy with photo coagulationNephropathy with dialysis: hemodialysis or peritonialCHD with stent installmentPeripheral vascular disease with metabolic and infection control, foot restNeuropathy symptomatis 49
50Complications: MacrovascularDM increases the risk of coronary artery disease, stroke, and peripheral vascular disease 2 to 4 times. Although controlling the glucose may be important early in the disease, controlling the BP and lipids, avoiding smoking, and taking ASA when indicated are much more important for prevention.
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52Complications: NeuropathyPresent in 60 - 70% of diabetics. Symmetric distal polyneuropathy is the most common type, and leads to Charcot joints, dislocations, fractures, ulcers, infections, and amputations.Prevention/Treatment: Control glucose, teach good foot care, do a foot exam yearly, refer to Podiatry if neuropathy or its complications are present, and control pain: tricyclics, topicals and anticonvulsants.53
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56Complications: MicrovascularNephropathyPresent in 20 - 40% of diabetics.Prevention/Treatment: Maintain BP 140/80, keep glucose at goal, and check urine albumin/creatinine ratio yearly. Use ACE inhibitor or ARB to treat BP.57
58Complications: MicrovascularRetinopathyPresent in 40 - 45% of diabetics.Prevention/Treatment: Control BP and glucose to previously mentioned goals, and refer to Ophthalmology for yearly screening exam/treatment.59Kriteria pengendalian
Are we doing a good job with treatment?Only 52.5% of diabetics have a HBA1C < 7%.Only 51.1% of diabetics have a BP < 130/80.Only 56.2% of diabetics have an LDL cholesterol < 100 mg/dl.Only 18.8% of diabetics are meeting all 3 goals!
Casagrande S.S. etal.Diabetes Care.2013;36:2271-2279.61Why do we do such a poor job?Patient reasons: Cost, side effects, fear of side effects, fear of injections, and denial of disease.Physician reasons: Clinical inertia - not enough time, not enough resources, concern about cost and pill burden, care directed at acute problems, and lack of knowledge of goals.62Health Maintenance Pneumovax once, then repeat after age 65.Hepatitis B vaccine now recommended by the ACIP/CDC.All other vaccinations as are appropriate for age.Routine dental exams.Contraception counseling for women of child bearing age.Age appropriate cancer screening only (the meaning of the increased risk of liver, pancreas, uterus, colon, breast and bladder cancers, and the decreased risk of prostate cancer, is unclear).
63First CaseA 61 year old woman comes to see you for a checkup after being told her BP elevated. She is asymptomatic. She has not seen a doctor in many years, and is on no prescription or other medications. She does not exercise or eat a healthy diet, and she does not smoke or drink. She has no health insurance. Her mother and 2 sisters have DM and HT.On PE her BP is 155/95, BMI of 40. Otherwise, her PE is normal.
What labs would you order at this point?64Who should be screened for DM?Everyone age 45 and over.
Everyone under 45 with a BMI 25 kg/m and one other risk factor for DM: Family history in a 1st degree relative. Race/ethnicity of Native American, African American, Latino, Asian American, or Pacific Islander. History of gestational DM or delivery of a baby 9 lbs. Polycystic ovary syndrome, HTN, lipid disorder, acanthosis nigricans, CVD or sedentary lifestyle.
If screening is normal, it should be repeated every 3 years.
ADA.Diabetes Care,2014;37(Suppl 1):S5-S80.
65First Case (cont)Lab Results Fasting glucose: 150 mg/dl Chol: 240 mg/dl TG: 250 mg/dl HDL: 36 mg/dl LDL: 154 mg/dl HBA1C: 8.8%
What diagnoses would you give her at this time?
66How do you diagnose DM? Fasting plasma glucose 126 mg/dl, or2 hour plasma glucose 200 mg/dl during an oral glucose tolerance test, orSymptoms of hyperglycemia and a random plasma glucose 200 mg/dl, orHBA1C 6.5%.
All should be repeated before making the diagnosis, unless 2 different tests are both consistent with DM.
ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.
67How do you diagnose pre-diabetes? Impaired Fasting Glucose (IFG): fasting plasma glucose 100 mg/dl and 125 mg/dl, orImpaired Glucose Tolerance (IGT): 2 hour plasma glucose 140 mg/dl and 200 mg/dl during an oral glucose tolerance test, orHBA1C 5.7 - 6.4%.
All should be repeated before making the diagnosis.
ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.
68Why and how should we treat pre-diabetes?It confers an increased risk of CVD, and without intervention, most will develop DM within 10 years.Aim for a weight loss of 5 - 10% and at least 150 minutes of moderate activity per week.Consider metformin for those with a BMI > 35, those who are younger than 60, and women with prior gestational diabetes.
Monitor at least yearly.
ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.
69First Case (cont)What treatment would you institute for this patient with newly diagnosed DM and a HBA1C of 8.8%?70How do you manage DM? Referral to a Diabetes Education Program to assist in education on Medical Nutrition Therapy (MNT), exercise, and all aspects of the disease, including treatment, self monitoring, complications, and the concept that it is a progressive disease leading to insulin therapy in most patients. Medication for glycemic control.Monitoring for complications.Treatment of HTN.Smoking cessation.Consider referral for bariatric surgery if BMI 35.
ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.71What are the glycemic goals? HBA1C < 7%.Fasting/Preprandial/Bedtime (AC and HS) capillary blood glucose (CBG) 70 - 130 mg/dl.Postprandial CBG 1 - 2 hours after starting a meal < 180 mg/dl.Goal is to achieve glycemic target without causing hypoglycemia.Reaching goal glycemia has been clearly shown to prevent microvascular complications; its effect on the prevention of macrovascular complications is less clear, but seems to be most important when attained early in the course of DM. Control of BP & lipids, use of ASA, and smoking cessation are essential in preventing CVD.
ADA.Diabetes Care, 2014;37 (Suppl 1):S5-S80.
72Does tight glycemic control prevent macrovascular disease? Based upon the findings of the UKPDS, ACCORD, ADVANCE and VADT trials, the ADA, AHA, and ACC issued a joint statement supporting the individualization of treatment goals, and stressing the importance of aggressive treatment and control early in the course of the disease.
Patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular and macrovascular complications, extensive comorbidities, or longstanding difficult to control DM, may reasonably have a HBA1C goal that is > 7%. Patients with a shorter duration of DM, a long life expectancy, and no significant complications, may reasonably have a HBA1C goal that is lower, < 7% or even < 6.5%.
Skyler etal.Diabetes Care.2009;32:187-192.73How do you choose medication for glycemic control?Choose based upon potency, safety, side effects, ease of use, effect on other risk factors, and cost. There is no good data yet showing that one class of medication prevents complications better than another, other than through the level of glycemic control and effects on other risk factors.74 Medications for DM: Biguanides - Metformin (Glucophage) - decrease hepatic glucose output - weight neutral or mild loss, no hypoglycemia, cheap - GI side effects, contraindicated in CRF and unstable CHF because of risk of lactic acidosis, B12 deficiency.
Sulfonylureas - Glipizide (Glucotrol), glimeperide (Amaryl) - enhance insulin secretion - cheap - weight gain, hypoglycemia. Insulins - Lispro (Humalog), aspart (Novolog), glulisine (Apidra); Regular; NPH; glargine (Lantus), detemir (Levemir); and fixed combinations - no dose limit, NPH and Regular are cheap, improve lipids - injections, weight gain, hypoglycemia, analogs are expensive. 75Medications for DM:(cont) Thiazolidinediones (TZDs or Glitazones) - Pioglitazone (Actos) - increase sensitivity to insulin - improve lipids, potential decrease in MI, no hypoglycemia - fluid retention, weight gain, CHF, fractures, bladder cancer (taken off of market in France and Germany). * DPP-4 Inhibitors - Sitagliptin (Januvia), saxagliptan (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina) - increase glucose-mediated insulin secretion, suppress glucagon secretion - weight neutral, no hypoglycemia - expensive, ?effects on immune system/pancreatitis/pancreatic cancer, long term effects not known.
GLP-1 Agonists (Incretin Mimetics) - Exenatide (Byetta, Bydureon), liraglutide (Victoza) - potentiate glucose-stimulated insulin secretion, suppress glucagon secretion, slow gastric motility - weight loss, ?delay/prevention of beta cell failure, no hypoglycemia - injections, expensive, GI side effects, ?pancreatitis/pancreatic cancer, ?medullary CA of the thyroid, long term effects not known.
76Other Medications for DM :
-Glucosidase Inhibitors - Acarbose (Precose), miglitol (Glyset) - reduce the rate of digestion of polysaccharides - weight neutral, no hypoglycemia - severe GI side effects, expensive, three times daily. Glinides - Nateglinide (Starlix), repaglinide (Prandin) - stimulate insulin secretion - weight gain, three times daily, expensive, hypoglycemia.
77How potent are these medications?*If initial HBA1C is 9%, use 2 medications. If initial glucose is 300-350mg/dl, or HBA1C is 10-12%, use insulin.
Medication Biguanides Sulfonylureas Insulin TZDs DPP - 4 Inhibitors GLP - 1 Agonists - Glucosidase Inhibitors Glinides Expected decrease in HBA1C
1.0 - 2.0 1.0 - 2.0 No limit 0.5 - 1.4 0.5 - 0.8 0.5 - 1.0 0.5 - 0.8 0.5 - 1.5 78First Case (cont)She was referred to the Diabetes Center for MNT and general teaching.She was started on metformin 500 mg twice daily, and was told to increase to 1000 mg twice daily after 2 weeks.She was referred to Ophthalmology.She was scheduled to return to clinic in 3 months for follow-up, with a HBA1C and a urine microalbumin/creatinine one week before her appointment.
Should any other medications be prescribed at this time?79What other disorders need treatment in patients with DM?In addition to treating the glucose, we must also treat the HTN, lipid abnormalities ACE Inhibitor (or ARB) for HTN, with a goal BP of 140/80 (per ACCORD tight control of HTN arm), although lower may be appropriate for some patients. Take at least one medication at bedtime. (*JNC 8 and ASH/ISH guidelines differ.)
Statin if above goal. Statin if overt CVD, or over age 40 with one or more other risk factors, regardless of baseline LDL. Goal LDL less than 100 mg/dl, and less than 70 mg/dl for overt CVD (or 30 - 40% below baseline). Treat TG if > 400 mg/dl. (*ACC/AHA guidelines use intensity of therapy rather than goals.)
Low dose ASA if overt CVD. Low dose ASA for men over 50 and women over 60 who have one or more other risk factors. Clopidogrel (Plavix) should be used in the case of ASA allergy.
ADA.Diabetes Care,2014;37(Suppl 1):S5-S80.80First Case (cont)Lisinopril 20 mg daily was added, and a BMP was ordered for 2 weeks.
Atorvastatin 40 mg daily was added, and lipids were ordered for one week before her 3 month appointment.
ASA 80 mg daily was added.81How do you monitor therapy? HBA1C level every 3 months if uncontrolled or if therapy is changed, otherwise every 6 months.Self monitoring of blood glucose is definitely indicated for patients on multiple daily doses of insulin, and may be indicated for patients on one dose of insulin daily, or on non insulin therapy particularly if there is a risk of hypoglycemia.82First Case (cont)She returns to clinic in 3 months. She has lost 5 kg.HBA1C is 6.1%, BP is 145/85, electrolytes were normal, Chol is 180 mg/dl, LDL is 68 mg/dl, HDL is 40 mg/dl, TG is 210 mg/dl, and she has no albuminuria.
HCTZ 25 mg daily is added.You are satisfied with her DM control.She is scheduled to return to clinic in 3 months with a BMP.83First Case (cont)She unfortunately does not return to see you for one year, but she has continued to take her medications as prescribed. She has gained 15 kg.Now her BP is 120/75, and HBA1C is 7.8%.
What medication adjustments, if any, do you make at this time?
84First Case (cont)You add glipizide ER 10 mg daily.You send her back to diabetes education to reinforce diet and exercise.She returns to clinic in 3 months with a HBA1C of 7.4%, an LDL at goal, and no albuminuria. She has lost 10 kg.What medication adjustments, if any, do you make at this time? 85First Case (cont)You add long acting insulin 10 units once daily. (She knows how to use insulin from giving it to her mother.)She returns to clinic in 3 months with a HBA1C of 6.0%. She has lost another 5 kg.You are happy with her control, and schedule her to return to clinic in 6 months with a HBA1C before.
86Second CaseThis is a 69 year old woman who has been followed elsewhere for DM for 15 years, HTN for 8 years, osteoporosis for 3 years, and hyperlipidemia for 5 years. She has had several episodes of hypoglycemia recently, usually after being late for a meal, and once in the middle of the night requiring an ER visit after a fall. She does not smoke or drink, lives alone, and has no family in town.Meds: Glybenclamide 5 mg daily, metformin 1000 mg twice daily, ramipril 10 mg daily, simvastatin 40 mg daily, ASA 81mg daily, alendronate 70 mg weekly, and calcium with vitamin D.87Second Case (cont)BP 128/78, BMI 35, fundi are normal, she has decreased sensation to filament exam on both feet, and the remainder of the PE is normal.She checks her CBGs AC breakfast and dinner, and they are 75-110 AC breakfast and 200 post dinner.HBA1C is 7.9%, but the remainder of her labs are normal.
What medication adjustments, if any, do you make?88Second Case (cont)Glybenclamide stopShe was referred to the Diabetes Educator to learn injection insulin rapid acting three times daily reinforce prior teaching.Follow-up HBA1C is 6.8%, her CBGs are at goal, and she has had no further episodes of hypoglycemia.She has also lost 10 kg.89Third CaseA 42 year old man with HTN, hyperlipidemia and an ischemic cardiomyopathy with an EF of 25% and severe SOB on minimal exertion, is referred to you by his cardiologist for management of fairly newly diagnosed DM. Meds: Metformin 500 mg twice daily, pioglitazone 15 mg daily, carvedilol 12,5 mg twice daily, furosemide 40 mg daily, lisinopril 20 mg daily, rosuvastatin 20 mg daily, and ASA 80 mg daily.
90Third Case (cont)BP 110/60, Wt 240 lbs, BMI 35, fundi difficult to visualize, elevated neck veins, S3 gallop, holosystolic murmur, 1+ edema, but foot exam was otherwise normal.He brings in a copy of recent labs: HBA1C 10.2%, FBS 252 mg/dl, Crt 1.8 mg/dl, and Ur Alb/Crt 50 mg/g (nl < 30).
What medication adjustments, if any, would you make?
91Third Case (cont)Metformin and pioglitazone were both discontinued .Insulin glargine 30 units daily was started, and he was sent to the Diabetes Educator to learn injection, self monitoring techniques, and self titration of insulin to reach a target FBS.He was also referred to Ophthalmology.He returned to clinic in 3 months on 45 units of insulin glargine daily with a glucose log showing fasting CBGs at goal, but a HBA1C of 7.9%.
92Third Case (cont)He then began checking AC and PC CBGs. The AC breakfast and dinner CBGs were at goal, but the AC lunch and PC CBGs were high, prompting the addition of 3 units of insulin lispro before breakfast and dinner. He was instructed on self titration of the insulin lispro, which was raised to 6 units at both times, resulting in AC and PC CBGs that were all at goal.A follow up HBA1C in 3 months was 6.8%.
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