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Diabetes

Mellitus

By Rozjanne Chrizsa A. Pahilan

CASE STUDY
• A 56-year-old Hispanic woman presents to
her medical practitioner with symptoms of
fatigue, increased thirst, frequent
urination, and exercise intolerance with
shortness of breath of many month’s
duration.
• She does not get regular medical care and
is unaware of any medical problems. Her
family history is significant for obesity,
diabetes, high blood pressure, and
coronary artery disease in both parents
and several siblings. She is not taking any
medications. Five of her six children had

CASE STUDY
• Physical examination reveals a BMI (body mass
index) of 34, blood pressure 150/90 mmHg and
evidence of mild peripheral neuropathy.
• Laboratory tests reveal a random blood sugar of
261 mg/dL; this is confirmed with a fasting plasma
glucose of 192 mg/dL. A fasting lipid panel reveals
a total cholesterol 264 mg/dL, triglycerides 255
mg/dL, high density lipoproteins 43 mg/dL, and low
density lipoproteins 170 mg/dL. What type of
diabetes does this woman have? What further
evaluations should be obtained? How would you
treat her diabetes?

Overview
• Pancreas is both an endocrine gland that
produces the peptide hormone insulin, glucagon,
and somatostatin and an exocrine gland that
produces digestive enzymes
• The peptide hormones are secreted from cells
located in the islets of Langerhans (β cells produce
insulin, α cells produce glucagon, and δ cells
produce somatostatin).
• These hormones play an important role in
regulating the metabolic activities of the body,
particularly the homeostasis of blood glucose.

Introduction

Diabetes
Mellitus

• refers to a group of common metabolic
disorders that share the phenotype of
hyperglycemia
• a heterogeneous group of syndromes
characterized by an elevation of blood glucose
caused by a relative or absolute deficiency of
insulin

Introduction • factors contributing to hyperglycemia include:  reduced insulin secretion  decreased glucose utilization  increased glucose production • DM is the leading cause of end-stage renal disease (ESRD). and adult blindness . nontraumatic lower extremity amputations.

Common Signs and Symptoms Unusual thirst Frequent Urination Weight change (gain or loss) Extreme fatigue or lack of energy Blurred vision Tingling or numbness in the hands or feet Frequent or recurring infections .

Common Signs and Symptoms Frequent or recurring infections Cuts and bruises that are slow to heal Feeling very tired much of the time Very Dry skin .

• TYPE 4: GESTATIONAL DIABETES MELLITUS . genetic defects or medications). Classification • TYPE 1: INSULIN DEPENDENT DIABETES • TYPE 2: NON-INSULIN DEPENDENT DIABETES • TYPE 3: OTHER (diabetes due to other causes for example.

polyphagia. and the type 1 diabetic shows classic symptoms of insulin deficiency (polydipsia. TYPE 1: INSULIN DEPENDENT DIABETES • characterized by an absolute deficiency of insulin caused by massive β-cell necrosis • As a result of the destruction of these cells. polyuria. . • Type 1 diabetics require exogenous insulin to avoid the catabolic state that results from and is characterized by hyperglycemia and life-threatening ketoacidosis. the pancreas fails to respond to glucose. and weight loss).

avoid ketoacidosis. This lasts for up to 15 minutes and is followed by the postprandial secretion of insulin. TYPE 1: INSULIN DEPENDENT DIABETES • CAUSE: In a normal postabsorptive period. low basal levels of circulating insulin are maintained through constant β-cell secretion. However. . A burst of insulin secretion occurs within 2 minutes after ingesting a meal. those with type 1 diabetes can neither maintain a basal secretion level of insulin nor respond to variations in circulating fuels TREATMENT: • A person with type 1 diabetes must rely on exogenous (injected) insulin to control hyperglycemia. and maintain acceptable levels of glycosylated hemoglobin (HbA1c) • The goal in administering insulin to those with type 1 diabetes is to maintain blood glucose concentrations as close to normal as possible and to avoid wide swings in glucose levels that may contribute to long-term complications. in response to transient increases in the levels of circulating glucose and amino acids. This suppresses lipolysis. proteolysis. and glycogenolysis. having virtually no functional β cells.

and peripheral insulin resistance. TYPE 2: NON-INSULIN DEPENDENT DIABETES • influenced by genetic factors. rather than by autoimmune processes or viruses.The β- cell mass may become gradually reduced in type 2 diabetes. obesity. aging. . • Type 2 diabetes is frequently accompanied by the lack of sensitivity of target organs to either endogenous or exogenous insulin.This resistance to insulin is considered to be a major cause of this type of diabetes. CAUSE: • The pancreas retains some β-cell function. but variable insulin secretion is insufficient to maintain glucose homeostasis .

However. most patients are dependent on pharmacologic intervention with oral glucose-lowering agents. β-cell function declines and insulin therapy is often required to achieve satisfactory serum glucose levels . TYPE 2: NON-INSULIN DEPENDENT DIABETES Treatment: The goal in treating type 2 diabetes is to:  Maintain blood glucose concentrations within normal limits and to prevent the development of long-term complications of the disease  Weight reduction. As the disease progresses. and dietary modification  decrease insulin resistance and correct the hyperglycemia of type 2 diabetes in some patients. exercise.

GESTATIONAL DIABETES • defined as carbohydrate intolerance with onset or first recognition during pregnancy. larger randomized studies are needed to fully assess neonatal outcomes and optimal dosing regimens . • Glyburide and metformin may be reasonably safe alternatives to insulin therapy for gestational diabetes. • Diet. However. and/ or insulin administration are effective in this condition. exercise.

Diagnosis .

1 mmol/L (200 mg/dL) 2 h after a 75-g oral glucose load • The current criteria for the diagnosis of DM emphasize that the FPG is the most reliable and convenient test for identifying DM in asymptomatic individuals .6 mmol/L (100 mg/dL) is considered normal  FPG = 5.6–6.0 mmol/L (126 mg/dL) warrants the diagnosis of DM • Based on the OGTT:  IGT is defined as plasma glucose levels between 7.1 mmol/L (140 and 199 mg/dL)  diabetes is defined as a glucose > 11.8 and 11.9 mmol/L (100–125 mg/dL) is defined as IFG  FPG > 7. Diagnosis • Glucose tolerance is classified into three categories based on the FPG:  FPG < 5.

Screening • Widespread use of the FPG as a screening test for type 2 DM is recommended because:  a large number of individuals who meet the current criteria for DM are asymptomatic and unaware that they have the disorder  epidemiologic studies suggest that type 2 DM may be present for up to a decade before diagnosis  as many as 50% of individuals with type 2 DM have one or more diabetes-specific complications at the time of their diagnosis  treatment of type 2 DM may favorably alter the natural history of DM • The ADA recommends screening all individuals >45 years every 3 years and screening individuals at an earlier age if they are overweight [body mass index (BMI) > 25 km/m2] and have one additional risk factor for diabetes • In contrast to type 2 DM. a long asymptomatic period of hyperglycemia is rare prior to the diagnosis of type 1 DM .

Screening .

and  (3) allow the patient to achieve as normal a lifestyle as possible  To reach these goals. the physician should:  identify a target level of glycemic control for each patient  provide the patient with the educational and pharmacologic resources necessary to reach this level  monitor/treat DM-related complications  Symptoms of diabetes usually resolve when the plasma glucose is <11.  (2) reduce or eliminate the long-term microvascular and macrovascular complications of DM. and thus most DM treatment focuses on achieving the second and third goals. LONG TERM TREATMENT  Overall Principles  The goals of therapy for type 1 or type 2 DM are to:  (1) eliminate symptoms related to hyperglycemia.1 mmol/L (200 mg/dL). .

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Insulin aspart. and Insulin glulisine (Rapid-acting) • Regular insulin (short-acting) • B. INSULIN PREPARATIONS • A. Intermediate acting insulin Examples: • Neutral protamine Hagedorn (NPH) insulin . Rapid-acting and short-acting insulin preparations Examples: • Insulin lispro.

. It is slower in onset than NPH insulin and has a flat. Long-acting Insulin Preparations Examples: • 1. Neither insulin detemir nor insulin glargine should be mixed in the same syringe with other insulins. leading to precipitation at the injection site and extending its action. prolonged hypoglycemic effect with no peak subcutaneously. because doing so may alter the pharmacodynamic and pharmacokinetic properties. Insulin glargine: The isoelectric point of insulin glargine (GLARQeen) is lower than that of human insulin. INSULIN PREPARATIONS • C. Slow dissociation from albumin results in long- acting properties similar to those of insulin glargine. This addition enhances association to albumin. Insulin detemir: Insulin detemir (deh-TEE-meer) has a fatty-acid side chain. • 2.

Insulin combinations • Various premixed combinations of human insulins. such as 70- percent NPH insulin plus 30-percent regular insulin (see Figure 24. are also available E.8). In contrast. . intensive treatment seeks to normalize blood glucose through more frequent injections of insulin (three or more times daily in response to monitoring blood glucose levels). The ADA recommends a target mean blood glucose level of 154 mg/dL or less (corresponding to a HbA1c of 7 percent or less) for patients with diabetes. 50 percent of each of these. Standard treatment versus intensive treatment • For patients with diabetes mellitus who require insulin therapy. standard treatment involves injection of insulin twice daily. and 75-percent NPL insulin plus 25-percent insulin lispro. and this is more likely to be achieved with intensive treatment. INSULIN PREPARATIONS D.

lipid. weight gain. protein synthesis. Interactions: Parenteral (SC or IV) Toxicity: Hypoglycemia. glycogen. and regulation of gene expression • Clinical applications: TYPE 1 & TYPE 2 • PK. lipodystrophy (rare) . INSULIN PREPARATIONS • MECHANISM OF ACTION: -Activate insulin receptor • Effects: -Reduce circulating glucose -promote glucose transport and oxidation. Toxicities.

• Patients with long-standing disease may require a combination of glucose-lowering drugs with or without insulin to control their hyperglycemia. • Patients who have developed diabetes after age 40 and have had diabetes less than 5 years are those most likely to respond well to oral glucose-lowering agents. . ORAL AGENTS: INSULIN SECRETAGOGUES • Useful in the treatment of patients who have type 2 diabetes but who cannot be managed by diet alone.

weight gain Examples: Glipizide. reduce circulating glucose● increase glycogen. because they promote insulin release from the β cells of the pancreas Mechanism Of Action: 1) Stimulation of insulin release from the β cells of the pancreas by blocking the ATP-sensitive K+ channels. Sulfonylureas • These agents are classified as insulin secretagogues. resulting in depolarization and Ca2+ influx 2) reduction in hepatic glucose production. Interactions : Orally active ● duration 10-24 h● Toxicity: Hypoglycemia. Effects:In px with functioning beta cells. Toxicities. and 3) increase inperipheral insulin sensitivity. Glyburide. far and protein information● gene regulation Clinical Applications: TYPE 2 Diabetes PK. Glimipiride .

Glinides • This class of agents includes repaglinide and nateglinide . However. Toxicities. Mechanism Of Action: Like the sulfonylureas. their action is dependent on functioning pancreatic β cells.Although they are not sulfonylureas. thereby initiating a series of reactions culminating in the release of insulin. Effects: In px with functioning beta cells. They bind to a distinct site on the sulfonylurea receptor of ATP-sensitive potassium channels. reduce circulating glucose● increase glycogen. the glinides have a rapid onset and a short duration of action. Interactions : >Oral● very fast onset of action● duration 5-8 hrs ●Toxicity: Hypoglycemian (Repaglinide) >Oral●Very fast onset and short duration (<4h)●Toxicity: Hypoglycemia (Nateglinide) . far and protein information● gene regulation Clinical applications: TYPE 2 DIABETES PK. They are particularly effective in the early release of insulin that occurs after a meal and are categorized as postprandial glucose regulators. they have common actions. in contrast to the sulfonylureas.

the biguanides and thiazolidinediones. These agents lower blood sugar by improving target-cell response to insulin without increasing pancreatic insulin secretion. ORAL AGENTS: INSULIN SENSITIZERS • Two classes of oral agents. improve insulin action. .

thereby decreasing insulin resistance. An important property of this drug is its ability to modestly reduce hyperlipidemia (low- density lipoprotein [LDL] and very-low-density lipoprotein [VLDL] cholesterol concentrations fall. is classed as an insulin sensitizer. . biguanide s  Metformin. Hypoglycemia may occur when metformin is taken in combination with insulin. • Mechanism of action: The main mechanism of action of metformin is reduction of hepatic glucose output. • Metformin may be used alone or in combination with one of the other agents as well as with insulin. It increases glucose uptake and use by target tissues. the only currently available biguanide. and high-density lipoprotein [HDL] cholesterol rises). largely by inhibiting hepatic gluconeogenesisMetformin also slows intestinal absorption of sugars and improves peripheral glucose uptake and utilization.

Toxicities. lactic acidosis (rare)● cannot use if impaired renal/hepatic function● Congestive heart failure (CHF). possibly pregnancy. alcoholism • Other uses: In addition to the treatment of type 2 diabetes. therefore. biguanide s • Effects: Decreased endogenous glucose production • Clinical applications: TYPE 2 DIABETES • PK. Interactions : • Oral●Maximal plasma concentration in 2-3 h • ●Toxicity: Gastrointestinal symptoms. metformin is effective in the treatment of polycystic ovary disease. Its ability to lower insulin resistance in these women can result in ovulation and. hypoxic/acidotic states. .

Thiazolidinediones (glitazones) • Another group of agents that are insulin sensitizers are the thiazolidinediones (TZDs). these drugs do not promote its release from the pancreatic β cells. so hyperinsulinemia is not a risk. also called the glitazones. • Although insulin is required for their action. • Troglitazone was the first of these to be approved for the treatment of type 2 diabetes but was withdrawn after a number of deaths from hepatotoxicity were reported. .

hypertriglyceridemia. Toxicities. Hyperglycemia. a nuclear hormone receptor. hepatic disease Examples: Pioglitazone and Rosiglitazone . Effects: Reduces insulin resistance Clinical Applications: Type 2 diabetes PK. hyperinsulinemia. long acting(>24h) Toxicity: Fluid retention. and elevated HbA1c levels are improved. and skeletal muscle. bone fractures in women. Ligands for PPARγ regulate adipocyte production and secretion of fatty acids as well as glucose metabolism. resulting in increased insulin sensitivity in adipose tissue. liver. weight gain. edema. cannot use if CHF. they are known to target the peroxisome proliferator–activated receptor- γ (PPARγ). Thiazolidinediones (glitazones) Mechanism of action: Although the exact mechanism by which the TZDs lower insulin resistance remains to be elucidated. macular edema. anemia. Interactions : Oral.

• Effects: Reduce conversion of starch and disaccharides to monosaccharides● Reduce post-prandial hyperglycemia • Clinical applications: TYPE 2 DIABETES • PK. thereby resulting in lower postprandial glucose levels. these drugs neither stimulate insulin release nor increase insulin action in target tissues. Both drugs exert their effects by reversibly inhibiting membrane-bound α-glucosidase in the intestinal brush border. Unlike other oral glucose-lowering agents. intestinal disorders • Examples: Acarbose. This enzyme is responsible for the hydrolysis of oligosaccharides to glucose and other sugars. the postprandial rise of blood glucose is blunted. Interactions : • Oral●Rapid onset • Toxicity: Gastrointestinal symptoms● cannot use if impaired renal/hepatic function. Miglitol . They act by delaying the digestion of carbohydrates. Consequently. ALPHA GLUCOSIDASE INHIBITORS Mechanism Of Action • These drugs are taken at the beginning of meals. Toxicities.

pancreatitis. Saxagliptin . Interactions : • Oral ● half-life-12 hr● 24 hr duration of action Toxicity: Rhinitis. slow gastric emptying. DIPEPTIDYL PEPTIDASE-IV • INHIBITORS Mechanism of Action:These drugs inhibit the enzyme DPP-IV. rare allergic reactions Examples: Sitagliptin. Toxicities. lowers glucagon levels. headaches. decreases appetite • Clinical applications: Type 2 Diabetes • PK. which is responsible for the inactivation of incretin hormones such as glucagon-like peptide-1 (GLP-1). Prolonging the activity of incretin hormones results in increased insulin release in response to meals and a reduction in inappropriate secretion of glucagon • Effects: Reduces post-meal glucose ● excursions: Increases glucose-mediated insulin release. Upper respiratory infections.

. • These agents may be used as adjunct therapy in patients who have failed to achieve adequate glycemic control on a sulfonylurea. The incretin effect occurs because the gut releases incretin hormones. INCRETIN MIMETICS. Incretin hormones are responsible for 60 to 70 percent of postprandial insulin secretion. in response to a meal. This effect is referred to as the “incretin effect” and is markedly reduced in type 2 diabetes. notably GLP-1 and glucose-dependent insulinotropic polypeptide. metformin. Glucagon-Like Polypeptide-1 (GLP-1) Receptor Agonist • Oral glucose results in a higher secretion of insulin than occurs when an equal load of glucose is given IV. a glitazone. or a combination thereof.

anorexia mild weight loss. Interactions : Parenteral (SC)● half-life-2. Increases glucose-mediated insulin release. pancreatitis Examples: Exenatide and Liraglutide . • Effects: Reduces post meal glucose excursions. Glucagon- Like Polypeptide-1 (GLP-1) • Receptor Agonist Mechanism of Action: The incretin mimetics are analogs of GLP-1 that exert their activity by acting as GLP-1 receptor agonists. INCRETIN MIMETICS. decrease food intake. slows gastric emptying. Consequently. and promote β-cell proliferation. decreases appetite • Clinical Applications: Type 2 Diabetes • PK. weight gain and postprandial hyperglycemia are reduced. lowers glucagon levels. vomiting.4 h Toxicity: Nausea. decrease postprandial glucagon secretion. headache. These agents not only improve glucose-dependent insulin secretion but also slow gastric emptying time. and HbA1c levels decline. Toxicities.

Type 1 and Parenteral ANALOG amylin:Binds meal glucose type 2 (SC)● rapid  Pramlintid to amylin excursions: diabetes onset● half- e receptors Lowers life.48 min+ glucagon Toxicity: levels. hypoglycemia decreases headache appetite BILE ACID Bile acid Lowers Type 2 Oral● 24-h SEQUESTRAN binder glucose diabetes duration of T through action  Colesevela unknown Toxicity: m HCl mechanisms Constipation. slows Nausea. indigestion. flatulence . applications Toxicities. emptying. Interactions AMYLIN Analog of Reduces post. OTHERS: (According to Katzung) Subclass MOA Effects Clinical PK. gastric anorexia.

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who have residual endogenous insulin production  reduce both fasting and postprandial glucose  Repaglinide and nateglinide are not sulfonylureas but also interact with the ATP-sensitive potassium channel  have the potential to cause profound and persistent hypoglycemia. LONG TERM TREATMENT • Insulin Secretagogues  stimulate insulin secretion by interacting with the ATP-sensitive potassium channel on the beta cell  most effective in individuals with type 2 DM of relatively recent onset (<5 years). a common side effect of sulfonylurea therapy . especially in elderly individuals  their use in individuals with significant hepatic or renal dysfunction is not advisable  Weight gain.

lactic acidosis  Metformin should be discontinued in patients who are seriously ill. improves the lipid profile. and in those receiving radiographic contrast material . LONG TERM TREATMENT • Biguanides  Metformin is representative of this class of agents  It reduces hepatic glucose production through an undefined mechanism and improves peripheral glucose utilization slightly  Metformin reduces fasting plasma glucose and insulin levels. in patients who can take nothing orally. and promotes modest weight loss  Gastrointestinal side effects:  Diarrhea  Anorexia  Nausea  metallic taste  The major toxicity of metformin.

LONG TERM TREATMENT • α-Glucosidase Inhibitors  Acarbose and Miglitol  reduce postprandial hyperglycemia by delaying glucose absorption. they do not affect glucose utilization or insulin secretion  reduce glucose absorption by inhibiting the enzyme that cleaves oligosaccharides into simple sugars in the intestinal lumen  The major side effects (diarrhea. abdominal distention) are related to increased delivery of oligosaccharides to the large bowel and can be reduced somewhat by gradual upward dose titration  This class of agents is not as potent as other oral agents in lowering the hemoglobin A1C but is unique because it reduces the postprandial glucose rise even in individuals with type 1 DM . flatulence.

receptor is found at highest levels in adipocytes but is expressed at lower levels in many other tissues  Thiazolidinediones promote a redistribution of fat from central to peripheral locations  Circulating insulin levels decrease with use of the thiazolidinediones.(peroxisome proliferator-activated receptor-) nuclear receptor  The PPAR. LONG TERM TREATMENT • Thiazolidinediones  reduce insulin resistance  bind to the PPAR. indicating a reduction in insulin resistance  Thiazolidinediones are associated with weight gain. and a mild increase in plasma volume  Peripheral edema and CHF may occur and is more common in individuals also treated with insulin  These agents are contraindicated in patients with liver disease or CHF (class III or IV) . a small reduction in the hematocrit.

some patients taking insulin secretagogues may require a reduction in those agents to prevent hypoglycemia . in fact. suppresses glucagon. and the brain  Exenatide increases glucose-stimulated insulin secretion. vomiting. the gastrointestinal tract. LONG TERM TREATMENT  Agents that Enhance GLP-1 Receptor Signaling  "Incretins" amplify glucose-stimulated insulin secretion  Agents that either act as a GLP-1 agonist or enhance endogenous GLP-1 activity have become available and are under development  Exenatide. and slows gastric emptying  Exenatide does not promote weight gain. most patients experience modest weight loss  It appears that GLP-1 agonists also suppress appetite  The A1C reductions with exenatide are modest compared to those with some oral agents  Agents that Enhance GLP-1 Receptor Signaling  Exenatide should not be used in patients taking insulin  The major side effects are nausea. is an analogue of GLP-1  Has prolonged GLP-1-like action by binding to GLP-1 receptors found in islets. and diarrhea.

for use with diet and exercise to improve glycemic control in adult individuals with type 2 DM  It can also be used in combination with metformin or a thiazolidinedione  Renal function should be assessed prior to initiation of sitagliptin therapy and periodically thereafter . sitagliptin. LONG TERM TREATMENT  Agents that Enhance GLP-1 Receptor Signaling  DPP-IV inhibitors represent a new class of oral agents that inhibit degradation of native GLP-1 and thus enhance incretin effect  These agents promote insulin secretion in the absence of hypoglycemia or weight gain. and appear to have a preferential effect on postprandial blood glucose  The FDA has approved the first DPP-IV inhibitor.

though it requires substantial expertise and is associated with the side effects of immunosuppression • Pancreatic islet transplantation has been plagued by limitations in pancreatic islet isolation and graft survival and remains an area of clinical investigation • Many individuals with long-standing type 1 DM still produce very small amounts of insulin or have insulin-positive cells within the pancreas • This suggests that beta cells are slowly regenerating but are quickly destroyed by the autoimmune process • Thus. EMERGING THERAPIES • Whole pancreas transplantation (performed concomitantly with a renal transplant) may normalize glucose tolerance and is an important therapeutic option in type 1 DM. efforts to suppress the autoimmune process and to stimulate beta cell regeneration are underway both at the time of diagnosis and in years after the diagnosis of type 1 DM • Closed-loop pumps that infuse the appropriate amount of insulin in response to changing glucose levels are potentially feasible now that continuous glucose-monitoring technology has been .

insulin secretagogues. transient worsening of diabetic retinopathy or neuropathy sometimes accompanies improved glycemic control . exenatide) therapies that improve glycemic control  increased economic costs  greater demands on the patient • As discussed previously. Complications of Therapy for Diabetes Mellitus • Side effects of intensive treatment include:  an increased frequency of serious hypoglycemia – most serious complication  weight gain – occurs with most (insulin. α. thiazolidinediones) but not all (metformin.glucosidase inhibitors.

diabetes. • Five of her six children had birth weight of over 9 pounds. • Family history is significant for obesity. increased thirst. • Does not get regular medical care and is unaware of any medical problems. • She is not taking any medications. CASE STUDY Subjective Data • symptoms of fatigue. and exercise intolerance with shortness of breath of many month’s duration. and coronary artery disease in both parents and several siblings. high blood pressure. . frequent urination.

Random blood sugar of 261 mg/dL. -Fasting lipid panel reveals: >a total cholesterol 264 mg/dL >triglycerides 255 mg/dL >high density lipoproteins 43 mg/dL > low density lipoproteins 170 mg/dL . CASE STUDY Objective Data • Physical Examination • Laboratory tests . -Fasting plasma glucose of 192 mg/dL.

• Further evaluations that should be obtained include HbA1c concentration dilated retinal examination. other risk factors are present. baseline laboratory tests. sulfonylureas. or nateglinide). insulin. or gestational diabetes. an additional agent such as insulin secretagogue (ie. and neurologic examination. or another antidiabetic medication could . CASE STUDY ANSWER • This patient has multiple risk factors for type 2 diabetes. Although she does not have a prior history of fasting hyperglycemia. The patient should be taught how to use a glucose meter and monitor her fingerstick blood glucose level. glucose intolerance. hygienic interventions (diet and exercise) and metformin would be first line of treatment. If she is unable to achieve adequate glycemic control on metformin. Assuming she has no renal or hepatic impairment. spot urine test for microalbumin/creatinine ratio. meglitinide. referred to a nutritionist for dietary instruction and given diabetes self-management education. plasma creatinine level.