Urgent Message: Diabetes mellitus is a common, complex and important condition frequently encountered in the urgent care setting. This article reviews current diagnostic criteria for diabetes and prediabetes and types of diabetes and discusses issues related to screening for diabetes and management issues relevant to urgent care. The authors previously reviewed the management of acute hyperglycemia in the July/August 2012 issue of JUCM.
Author: Anthony J. Pick, MD, CDE and David L. Pick, MD, FAAFP
Anthony J. Pick is Assistant Professor of Endocrinology and Medicine, Clinical, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
David L. Pick, MD, FAAFP, is Founding member Urgent Care College of Physicians, Founding Board.
Conflicts of Interest: David L. Pick has no conflicts of interest to report. Anthony J, Pick is on the Speakers’ Bureaus for Takeda (pioglitazone), Novo Nordisk (liraglutide, analog insulins), Sanofi (glargine and glulisine), Eli Lilly (linagliptin, analog insulins), Janssen Pharmaceuticals (canagliflozin), Bristol Myers Squibb and Astra Zeneka (exanatide, Onglyza).
Diabetes Definition and Basic Pathophysiology
Diabetes mellitus describes several diseases of metabolism with chronic hyperglycemia and disturbances of carbohydrate, lipid, and protein metabolism. There is relative or absolute insulin deficiency and varying degrees of underlying insulin resistance (primarily in liver and muscle). Type 1 diabetes has autoimmune destruction of beta-cells and usually results in profound insulin deficiency. In Type 2 diabetes, there are also changes described in brain regulation, gut hormones (incretins), alpha cells (excess glucagon secretion) kidney (changes in renal glucose clearance) and fat cell metabolism (“the ominous octet”).1 Other causes of diabetes are reviewed below.
Diagnosing Diabetes Mellitus
Diagnostic criteria for diabetes mellitus have been defined and refined by various groups, such as the World Health Organization, American Diabetes Association, and the European Diabetes Epidemiology Group. The diagnosis is now based on one of four abnormalities: random elevated glucose with symptoms, fasting plasma glucose, an abnormal oral glucose tolerance test or elevated hemoglobin A1c. The definitions are related to the association between blood glucose levels and risk of retinopathy. The American Diabetes Association issued diagnostic criteria for the diagnosis of diabetes mellitus in 1997 with the latest follow up in 2010.2
Diabetes is diagnosed based on classic symptoms of hyperglycemia (thirst, polyuria, weight loss, blurry vision) and a random blood glucose value ≥ 200mg/dl, and confirmed on another occasion. Fasting (no calorie intake for at least 8 hours) plasma glucose (FPG) levels ≥ 126 mg/dl (7 mmol/L), 2- hour post- 75-g oral glucose challenge values ≥ 200 mg/dL (11.1 mmol/L) and A1c levels ≥ 6.5%. Diabetes also can be diagnosed in asymptomatic individuals. An abnormal result should be confirmed by repeat measurement of the same test. In any one individual, there can be discordance between the different criteria. If there is discordance, the test diagnostic for diabetes should be repeated. If two different tests are concordant for diabetes, no additional testing is needed. An HbA1c value below 6.5% does not exclude diabetes (Table 1). Overall, the A1c and FPG criteria resulted in the same classification for 98% of the studied population. The diagnosis of diabetes with an HbA1c should be confirmed with a repeat value. If the HbA1c level is unreliable (such as with rapid red cell turnover with anemia or hemoglobin genetic variants), then the other diagnostic criteria should be used.3-5
Prediabetes, Impaired Glucose Tolerance and Impaired Fasting Glucose
Pre-diabetes represents an elevation of plasma glucose above the normal range but below that for clinical diabetes. Patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or intermediately abnormal HbA1c levels are at increased risk of developing diabetes. The natural history of IGT and IFG can be variable. However, about 25% of subjects will progress to diabetes over 3 to 5 years.6
A normal fasting blood glucose is below 100 mg/dL. IFG is defined as a fasting blood glucose ≥ 100 mg/dL to 125 mg/dL (5.6-6.9 mmol/L). IGT is defined by a 2-hour post 75g oral glucose tolerance test (OGTT) at or above 140 mg/dL to 199 mg/dL (7.8-11.0 mmol/L). HbA1c levels between 5.7 and 6.4% (6.0-6.4% per the International Expert Committee) also define a category of increased risk of diabetes onset. There is a clear association between pre-diabetes, metabolic syndrome, and diabetes. Cardiovascular risk likely is increased, probably mediated by factors related to the underlying metabolic syndrome. Weight loss and increased physical exercise is desirable and may help prevent the onset of diabetes. Control of associated cardiovascular risk factors (lipids, blood pressure) should be strongly considered. There is ongoing controversy about the definition and significance of prediabetes because in many people, prediabetes may not progress to diabetes, whereas other patients may be at risk of developing diabetes.7,8
Classification of Diabetes Mellitus
The 1997 American Diabetes Association (ADA) Expert Committee introduced the terms Type 1 and Type 2 diabetes and recommended against terms such as insulin-dependent, non-insulin dependent, juvenile-onset, maturity-onset, and adult-onset diabetes. In addition to Type 1 and Type 2 diabetes, specific types of diabetes are identified: Gestational diabetes (onset associated with pregnancy) and diabetes secondary to recognized genetic defects, diseases of the exocrine pancreas, other endocrinopathies, or drugs (Table 1). Type 2 diabetes accounts for more than 90% of cases of diabetes in the United States, Canada, and Europe; Type 1 diabetes accounts for 5% to 10% and the remainder is a result of other causes. Type 1 diabetes is due to autoimmune destruction of the pancreatic beta cells. There is a subtype that is idiopathic and not clearly autoimmune (type 1B diabetes mellitus).
Patients with type 1 diabetes may be overweight or obese and have superadded insulin resistance. Another sub-type of type 1 diabetes is latent autoimmune diabetes in adults (LADA), which may produce progressive decline in insulin secretion over time and have markers of autoimmunity detectable, if sought. Type 2 diabetes has underlying variable degrees of insulin resistance and insulin deficiency. A complex and individually variable polygenic process likely is present, with added environmental influences (sedentary lifestyle, excess calorie intake, central weight gain). Other causes of diabetes include discrete genetic disorders, exocrine pancreatic diseases, hemochromatosis, endocrinopathies and medications. Examples of discrete genetic disorders include maturity onset diabetes of the young (MODY) syndromes that have onset in those younger than age 25, non-insulin dependent, autosomal-dominant, and diabetes with no evidence of islet autoimmunity. A number of specific phenotypes and gene mutations have been identified (HNF-1, HNF-4, glucokinase and others). Exocrine pancreas disorders such as post pancreatic surgery, chronic pancreatitis, and cystic fibrosis lead to diabetes.
There is often insulin and glucagon deficiency that leads to both hyper- and hypoglycemia risk. Endocrine disorders that can cause diabetes include Cushing’s syndrome, acromegaly, pheochromocytoma, glucagonoma, somatostatinomas, and hyperthyroidism. Medications that can provoke onset of diabetes include glucocorticoids, statins, beta-blockers, thiazide diuretics, nicotinic acid, diazoxide, dilantin, alpha interferon, pentamadine, vacor, somatostatin and atypical antipsychotic agents (Table 2). Glucorticoid-induced diabetes is likely the most common cause of medication-induced diabetes. The mechanisms by which glucocorticoids induce diabetes are complex and include increased insulin resistance and adverse beta-cell effects. The effect is often reversible. Recent literature implicates statin use in onset of diabetes on the order of 220 patients treated to cause 1 new case of diabetes. Importantly, this does not affect the positive cardiovascular effects of statin use.9
Diabetes Screening
Should urgent care facilities screen for diabetes, prediabetes or poorly controlled diabetes? Type 2 diabetes is very common, has been increasing in prevalence, is often not diagnosed until complications appear, and up to one-third of patients with diabetes may not be diagnosed. Prediabetes and diabetes are conditions in which early detection is valuable because it is common, duration of disease is a predictor of adverse outcomes, and effective interventions are widely available and can prevent disease progression and reduce complications. Many patients with prediabetes or diabetes likely will present to an urgent care facility or emergency room as their sole source of contact with the medical system. It is, therefore, reasonable to consider screening for diabetes in urgent care. Tools for screening for undiagnosed diabetes or prediabetes include risk factor analysis (such as first-degree relative with diabetes, member of a high-risk ethnic group, prior history of gestational diabetes, history of polycystic ovarian syndrome); clinical features (body mass index, acanthosis nigricans as a skin maker of insulin resistance, female hirsutism), random blood glucose levels and Hba1c level. A patient’s clinical presentation also may be a clue to underlying glucose tolerance, such as perianal abscess, other soft-tissue infections, possibly fungal infections (including balanatis, vaginitis), and renal stones and vascular events.10,11
Glycohemoglobin testing for diagnosis of diabetes has the advantages of not requiring fasting and the test can be done at any time. A glycohemoglobin level is a powerful tool to detect and stratify glucose control over the prevailing 3 months in the outpatient and inpatient arena. In an urgent care setting, blood glucose levels often will be affected by recent food intake and stress from acute illness and may not be suitable for diagnosis of diabetes.
Literature exists regarding use of point-of-care blood glucose levels and/or glycohemoglobin levels to screen for diabetes or prediabetes in an acute care setting. In a Los Angeles, California, urban emergency department study, a substantial number of patients were at risk of undiagnosed diabetes (11%) and prediabetes (55%). All patients with two risk factors (members of a high-risk racial or ethnic population [African American, Hispanic, Native American, Asian American, or Pacific Islander]; age ≥45 years; estimated body mass index ≥25 kg/m2; medication-treated hypertension; medication-treated hyperlipiemia; family history of first-degree relative with diabetes; history of gestational diabetes; history of vascular disease; history of elevated blood glucose; polyuria and polydipsia; weight loss ≥ 10 lb within the previous 3 months or soft-tissue infection) and a random blood serum glucose >155 mg/dL were later diagnosed with diabetes or prediabetes.12-14
A glycohemoglobin level also will help discriminate between stress-induced hyperglycemia and underlying diabetes and between recent good glycemic control versus poor glucose control in patients with known diabetes. However, glycohemoglobin testing from a reference laboratory will likely not be available at the time of service and will add an extra administrative and potentially medico-legal burden because a follow-up process will be needed. An abnormal point-of-service glycohemoglobin will likely require follow up and confirmation from a reference laboratory. Undiagnosed diabetes is common and serious so it is reasonable to consider whether urgent care facilities should contribute to the detection of diabetes as a service to the individuals screened and the community. Downsides to screening for diabetes with a glycohemoglobin level include the added cost for the additional testing, a requirement to provide referral for suitable follow up and futility if the patient has no current interest in detecting or managing diabetes. Patients could provide informed consent for proceeding with glycohemoglobin testing. Issues related to screening for diabetes, prediabetes, and poorly controlled diabetes in the urgent care setting are an important area for further research.
Estimated Average Glucose
The estimated average glucose converts the hemoglobin A1c (a 2- to 3-month blood glucose average) to a value using the same units as patients and physicians use with blood glucose meters or laboratory studies (mg/dL or mmol/L). The relationship between A1C and eAG is described by the formula 28.7 X A1C – 46.7 = eAG. The use of eAG may help patients better understand how well their diabetes is under control. For example, an HbA1C of 7% (the current American Diabetes Association control goal) is an eAg of 154 mg/dL. An HbA1c of 9.5% is an eAg of 226 mg/dl (Table 1).15
Managing Diabetes
The goals of treatment of diabetes include prevention of hypoglycemia and excess chronic hyperglycemia and long-term prevention of microvascular and macrovascular disease. In many patients, the goal of glucose control is to attain and maintain glycohemoglobin levels below 7%.16
Table 2 summarizes the available non-insulin glucose-lowering agents. Table 3 summarizes kinetics of specific insulin preparations in the United States. It is relevant for urgent care physicians to be familiar with all diabetes-related agents, understand the basic mechanism of action and be aware of potential side effects with which patients may present to an urgent care clinic.
Current guidelines indicate that metformin (a biguanide) is the first-line choice of oral agent for diabetes. It is effective, inexpensive, and familiar to physicians and is likely the most widely prescribed diabetes oral agent. The major target of metformin is the enzyme AMP-activated protein kinase and activation by metformin results in a decrease of liver glucose production and increased glucose transport in skeletal muscle. The most frequent adverse effects are nausea, decreased appetite, abdominal discomfort, and diarrhea. There is a small incidence of hypoglycemia with metformin monotherapy (at or less than 3% range). Long term metformin use has been associated with vitamin B12 deficiency. The most feared side effect is lactic acidosis. The incidence is rare (3 per 100,000 patient years) and has mostly been reported where metformin use is contraindicated (advanced renal, liver, pulmonary and cardiac dysfunction.) The Cochrane review suggests metformin is not directly associated with lactic acidosis.17 Current radiology guidelines recommend withholding metformin 48 hours after intravenous contrast administration or until no change in renal function is confirmed. Of interest, a review of this issue found contradictory guidelines in the literature and a lack of evidence to support the available guidelines. Ordering computed tomographic scans with contrast is commonly done by urgent care physicians in patients with diabetes taking metformin, so familiarity with this issue is important. Medico-legally we recommend erring on the side of conservative practice in urgent care until further data are available. Hypoglycemia associated with use of metformin is rare (2.4%-3% range) and is usually minor.
Sulfonylureas also are widely prescribed for Type 2 diabetes. They have a rapid onset of action and are inexpensive. Sulfonylureas work by inducing insulin secretion by binding to potassium ATP channels in the beta cell. There is significant risk of hypoglycemia, including prolonged hypoglycemia. Older-generation sulfonylureas may be cardiotoxic (blunt ischemic preconditioning of the myocardium) or possibly pro-arythmogenic. Sulfonylureas also are associated with weight gain and secondary failure due to accelerated beta-cell burn-out. Certain sulfonylureas have been associated with syndrome of inappropriate antidiuretic hormone secretion, phototoxicity, hemolysis, hepatitis and allergic reactions (such as chlorpropamide). Chlorpromide and glyburide have also been associated with disulfuram-like reactions to alcohol use.
Pioglitazone (Actos) is the only remaining member of the thiazolidinediones drug class. Rezulin (troglitazone) was withdrawn because of severe liver injury) and Avandia (rosiglitazone) has restricted availability because of data supporting increased risk of myocardial infarction. Thiazolidinediones act by activating peroxisome proliferator-activated receptor gamma (PPAR-gamma) nuclear transcription factor receptors. This results in complex gene effects in carbohydrate and lipid metabolism, including enhanced insulin sensitivity in liver and muscle. Actos has been associated with fluid retention and, therefore, can precipitate heart failure in at-risk patients. Its use is contraindicated in patients with NYC class 3 and 4 heart failure. Actos has also been associated with weight gain and increased risk of long bone fractures in postmenopausal women. There is a recent association with a small increased risk of bladder carcinoma.18 Actos is contraindicated in patients with active bladder carcinoma. Actos has a low intrinsic risk of hypoglycemia but will increase a patient’s risk of hypoglycemia when used in conjunction with other agents, especially sulfonylureas and/or insulin. Insulin use with Actos increases risk of edema and fluid retention.
Dipeptidyl dipeptidase 4 (DDP4 inhibitors result in increased endogenous GLP-1 levels due to inhibition of the native GLP-1 degradation enzyme. GLP-1 has positive effects on glucose metabolism with a glucose-dependent increase in insulin secretion and decreasing hepatic glucose output by decreasing excess alpha cell glucagon secretion. Three agents in this class are approved in the United States (sitagliptin (Januvia), Vildagliptin (Onglyza) and linagliptin (Tradjenta). These agents are dosed daily and are likely gaining in popularity by prescribers because they are once-daily, well tolerated, have a low incidence of hypoglycemia, are widely promoted and not thought to lead to accelerated beta-cell failure. Cardiovascular safety studies are in progress but data to date are reassuring. The most common adverse events reported are increased nasopharyngitis, upper respiratory tract infection and headaches. It is not clear if there is an adverse effect on the immune system. There are rare reports of pancreatitis. It is not yet clear if there is a rare causal relationship with pancreatitis beyond the increased risk associated with Type 2 diabetes. Severe central abdominal pain, nausea, and vomiting should prompt consideration and evaluation for pancreatitis. If pancreatitis is confirmed in patients taking a DDP4 inhibitor, an adverse drug report to the FDA is indicated.
Three GLP-1 analogues are available in the United States and are given by subcutaneous (SQ) injection. Byetta (exanatide) given twice daily was the first to market. This was followed by (Victoza (liraglutide) given daily and Bydureon (given weekly), which was recently approved. These agents resist degradation by DDP4 enzyme and provide pharmacological levels of GLP-1 hormone. They increase insulin secretion in a glucose-dependent manner (low intrinsic risk of hypoglycemia), decrease glucagon secretion and decrease hepatic glucose output, slow gastric emptying and increase satiety (associated with weight loss) (Table 2). The most common side effect is nausea and occasional emesis. These agents, like DDP4 inhibitors, have a rare association with pancreatitis. Causality has also not been confirmed. Labeling for Victoza and Bydureon includes an FDA boxed warning regarding increasing the incidence of medullary thyroid carcinoma in rodents. It is not known if there is an increased risk of medullary thyroid carcinoma in humans. These agents can be associated with hypoglycemia if used with sulfonlyureas, meglitinides or insulin. Bydureon can cause SQ nodules at the injection site that are transient and due to a foreign body reaction to the carrier that extends the action of exanatide.
A new class of agents for management of type 2 diabetes has recently been approved. Canagliflozin (Invokana) from Janssen Pharmaceuticals is a first in class inhibitor of the sodium glucose 2 transporters (SGL2). This medication results in increased urinary glucose excretion and has a low intrinsic risk of hypoglycemia. This medications lowers blood glucose and is associated with blood pressure reduction and weight loss in the 3% of body weight range. Side effects include an osmotic diuresis with possible thirst, increased urination, blood pressure reduction, presyncope, syncope or orthostasis. This is more likely in the elderly. The effect on volume status can increase potassium and serum creatinine levels. Additional side effects include an increase in LDL cholesterol levels and an increased incidence of genital fungal infections and urinary tract infections.
The effects and side-effects of the other available diabetes agents are summarized in Table 1.19
Hypoglycemia
Drugs are the most frequent cause of hypoglycemia in adults. Insulin and sulfonylureas are the leading cause of drug-induced hypoglycemia by far. Mechanisms of drug-induced hypoglycemia include stimulating insulin release, reducing insulin clearance, and interfering with glucose metabolism. Some drugs will potentiate the hypoglycemic effects of diabetes agents. Drug-induced hepatotoxicity, renal toxicity or pancreatitis may lead to hypoglycemia. Alcohol and herbal remedies can cause hypoglycemia and are not discussed further here. Drug-induced hypoglycemia as a cause of acute medical admissions ranges from 0.1% to 7%. The median length of hospital stay was 4 days.20 One survey showed that 20% of hospital admissions for adverse drug reactions were related to hypoglycemia.21
Hypoglycemia is a common adverse effect of insulin treatment and a limiting factor for control of Type 1 diabetes. Patients with Type 2 diabetes (with or without insulin treatment) also may experience hypoglycemia. It can be disruptive with loss of work productivity, costly, induce patient fear, and also limit glycemic management. Hypoglycemia in patients with Type 2 diabetes may also cause morbidity and excess mortality.22
Budnitz et al reported a survey of emergency room visits for adverse drug events in 12,666 cases of older adults.22 Antidiabetic drugs were the second most prevalent drug category and 94.6% of adverse reactions were related to hypoglycemia. These findings extrapolated to 54,000 total emergency visits per year in the United States, with nearly 23,000 leading to a hospital stay. Insulin accounted for 13.9% of overall hospital admissions from adverse drug reactions, and 10.7% from oral antidiabetic agents. Sulfonylureas are the diabetes treatment oral agent class most responsible for causing hypoglycemia. Other non-diabetes-related drugs are occasionally associated with hypoglycemia, including nonsteroidal anti-inflammatory drugs, antimalarials (pentamadine), antifungals, anti-seizure medications, antibiotics (such as quinolones, trimethoprim-sulfamethoxazole), and beta-blockers (and may delay recovery from hypoglycemia)
Sulfonylureas with prolonged half-lives, such as glyburide, chlorpropamide and glibenclimide are likely to have a higher incidence and longer duration of hypoglycemia. Advanced age and underlying renal and liver disease increase the risk of hypoglycemia, such as from insulin or oral agents.
Alpha-glucosidase inhibitors delay digestion and absorption of disaccharides, such as sucrose. Patients who develop hypoglycemia (such as from concomitant use of insulin or a sulfonylurea) while taking these agents should treat the hypoglycemia with a monosaccharide such as glucose or glucagon.
Every urgent care clinic should have a protocol for treatment of hypoglycemia, especially if severe. There should be strong consideration of having glucagon and intravenous dextrose available. The ADA recommends 15 to 20 g of carbohydrate for treatment of hypoglycemia, in the form of 3 to 4 glucose tables, 4 oz juice or regular soda, 2 Tbsp raisins, or 4 to 5 saltines with 1 Tbsp oney or corn syrup.
Conclusion
Diabetes mellitus is a complex, heterogeneous, common and important group of disorders. Patients with diabetes often present to urgent care clinicians, either incidentally, because of a complication from diabetes, or after experiencing a side effect of diabetes treatment. We have reviewed current diagnostic criteria for diabetes (including fasting blood glucose levels above 126 mg/dL (in the non-stressed state), random blood glucose levels above 200 mg/dL (with hyperglycemia symptoms), based on an abnormal standardized OGTT or a glycohemoglobin (HbA1c) above 6.5% from a reference laboratory). We also reviewed the classification of causes of diabetes (the vast majority being from Type 2 diabetes (~90%), followed by Type 1 diabetes (~5-10%) and other rarer causes. We also discussed screening issues for urgent care and reviewed management issues relevant to urgent care physicians. Pancreatitis is a conceivable, but if associated at all, rare complication of DDP4 and GLP-1 analog therapy. Pioglitazone (Actos) may cause fluid retention and weight gain and precipitate heart failure in vulnerable patients. Metformin is usually safe and effective but can be associated with gastrointestinal side effects and there is a lingering (possibly incompletely justified) concern about lactic acidosis. Suitable precautions should be followed in patients on metformin who are exposed to intravenous contrast material, mainly from the medico-legal point of view. Hypoglycemia related to insulin and sulfonylurea use likely will be the the most common, and potentially the most serious, diabetes treatment related side effect seen in urgent care.
Table 1 (reference 15)
The American Diabetes Association goal for glycohemoglobin (HbA1c) levels is<7%. This level is chosen to lower the risk of long-term diabetes complications such as problems with the eyes, nerves and kidney.) This is an estimated average glucose (eAG*) below 154 mg/dL.
| A1C | eAG | |
| % | mg/dL | mmol/L |
| 6 | 126 | 7.0 |
| 6.5 | 140 | 7.8 |
| 7 | 154 | 8.6 |
| 7.5 | 169 | 9.4 |
| 8 | 183 | 10.1 |
| 8.5 | 197 | 10.9 |
| 9 | 212 | 11.8 |
| 9.5 | 226 | 12.6 |
| 10 | 240 | 13.4 |
Table 2 Available Non-Insulin Glucose Controlling Agents for Diabetes Mellitus (Highlighting Side Effects Potentially Relevant to Urgent Care Providers)
| Oral Agents | Mechanism of action | Urgent Care Relevant side effects |
| Sulfonylureas* | Induce insulin secretion | Hypoglycemia |
| Meglitinides | Induce insulin secretion, short acting | Hypoglycemia |
| Biguanides (metformin) | Decrease hepatic glucose output | GI side effects, lactic acidosis (rare) |
| TZD | Insulin sensitization | Edema, CHF, fracture, ? bladder carcinoma |
| Alpha glucosidase inhibitors | Slow disaccharide digestion | GI, may blunt hypoglycemia Rx if not glucose |
| DDP-4 inhibitors** | Increase endogenous GLP1, GIP | Pancreatitis (rare), URI, UTI |
| Bromocriptine QR | Dopamine agonist, CNS effect | Nausea, emesis, orthostasis |
| Colesevelam | Bile acid sequestration | Constipation |
| SGL2 inhibitor | Increase urine glucose excretion | Hyperkalemia, dehydration, UTI, genital mycotic infection |
| Subcutaneous (non insulin) agents | ||
| Pramlintide | Amylin analog | Hypoglycemia combined with insulin or SU, meglitinide |
| GLP1 analogs*** | Activate GLP1 receptors | Pancreatitis (rare), decreased renal function, nausea, local reaction |
*First generation SU, glyburide associated with prolonged hypoglycemia, especially elderly and may have cardiotoxicity (increased arythmia and increased coronary ischemia by blocking ischemic preconditioning). Chlorpropamide can cause SIADH.
** sitagliptin(Januvia, Merck Inc.), xxgliptin (Onglyza, Onglyza met XR, BMS), linagliptin (Trajenta, Eli Lilly and Boehringer Mannheim, Inc.), Nesina (alogliptin, Takeda)
*** (exanatide (Byetta, Amylin Pharmaceuticals) , liraglutide (Victoza, Novo Nordisk), Bydureon (extended release exanatide)
Combination medications: These include Actoplusmet, Duetact, Onglyza XR, Combisync), Tradentadueto, Oseni, Kazano and others that combine above noted drug classes
Table 3
Pharmacokinetics of SQ Insulin Preparations*
| Insulin | Onset | Peak | Duration |
| Rapid-acting analogs | 5-15 min | 2-3 hours | 6-10 hours |
| Regular | 30-60 min | 2-3 hours | 6-10 hours |
| NPH | 2-4 hours | 4-10 hours | 12-18 hours |
| Glargine | 2 hours | No peak | 12-24 hours |
| Detemir | 2 hours | No peak | 12-24 hours |
* Renal failure leads to prolonged insulin action and altered kinetics
Premixed insulins available include 70/30, Humalog 75/25 and Novolog 70/30 mix, Humalog 50/50
High concentration specialty insulins: u-500*
SQ = subcutaneous
References
- Ralph A. De Fronzo. Banting Lecture. From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes. Vol. 58, April 2009. 773-795.
- Diagnosis and classification of diabetes mellitus, Author American Diabetes Association, Diabetes Care 2010;33 Suppl1:562
- International Expert Committee. International Expert committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327
- Bennett CM, Guo M, Dharmage SC. HbA(1c) as a screening tool for detection of Type 2 diabetes; a systematic review. Diabetes Medicine 2007;24:333
- Buell C, Kermah D, Davidson MB. Utility of A1c for diabetes screening in the 1999-2004 NHANES population. Diabetes Care 2007;30:2233
- Nathan DM, Davidson MB, DeFronzo RA et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care 2007:30:753.
- Pre-Diabetes, Metabolic Syndrome, and Cardiovascular Risk. Scott M. Zgrundy, Journal of American College of Cardiology. Vol. 59,No. 7, 2012. 635-43.
- Prediabetes: a high-risk state for diabetes development. Adam G. TAbak, Christian Herder, Wolfgang Rathmann, Eric J Brunner, Mika Kivimaki. Lancet, 2012;379:2279-90.
- NEJM
- Increased Risk of diabetes following perianal abscess: a population-based follow-up study. Po-Li Wei et al. Int. J. Colorectal Disease DOI 10.1007/s00384-012-1519-2
- Increased Risk of Diabetes in Patients with Urinary Calculi: A 5-Year Follow up Study. The Journal of Urology Vol. 186,1888-1893, November 2011.
- Detection of Undiagnosed Diabetes and Prediabetic States in High-risk Emergency Department Patients. Academic Emergency Medicine 2009;16:394-402.
- Point-of-care Glucose and Hemoglobin A1c in Emergency Department Patients without Known Diabetes: Implications for Opportunistic Screening. Academic Emergency Medicine 2008; 15:1241-1247.
- Hemoglobin A1c as a Screen for Previously Undiagnosed Prediabetes and Diabetes in an Acute-Care setting. Diabetes Care. 34:1908-1912,2011.
- Translating the A1c Assay Into Estimated Average Glucose Values. Diabetes Care 31:1-6,2008. David Nathan et al.
- Silvio E. Inzucchi et al. Management of Hyperglycaemia in Type 2 Diabetes: A Patient-Centered Approach. Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, Volume 35., June 2012:1364-79
- Cochrane review citation
- Bladder cancer reference
- Comparative Effectiveness and Safety of Medications for Type 2 Diabetes: An Update Including New Drugs and 2-Drug Combinations. Annals of Internal Medicine. 2011;154:602-613.
- Drug-drug interactions amongst elderly patients hospitalized for drug toxicity JAMA 2003 April 2, 289(13): 1652-8).
- Drug-Induced Hypoglycaemia. An Update. Chaker Ben Salem et al. Drug Safety 2011;34(1)21-45).
- Hypoglycaemia: a therapeutic concern in type 2 diabetes. Alan J. Garber. Lancet. Vol. 379, June 16, 2012, 2215-6).
- Budnitz et al. (Reference: Emergency Hospitalizations for Adverse drug events in older Americans NEJM. 2011;365:2002-12.