After diagnosis of diabetes, the importance of protecting the body from damage caused by hyperglycemia cannot be overstated. It is commonly recommended that T2DM patients who use insulin self-monitor their blood glucose levels, but the evidence to support the effectiveness of this practice is inconclusive. It is important to establish individual goals with patients regarding target blood glucose measurements. HbA1c measures nonreversible glycosylation of the hemoglobin molecule, which is directly related to blood glucose concentrations. Traditionally it has been recommended that therapy be adjusted to maintain HbA1c values near or less than 7% in nonpregnant adults.
When considering appropriate pharmacologic therapy, a major factor to consider is whether the patient is insulin deficient, insulin resistant, or both.
Available since the late 1950s, metformin can trace its roots back to medieval Europe, where biguanides in the form of French lilac were used in diabetes treatment. Metformin is well tolerated, with the most common side effect being gastrointestinal (GI) complaints, such as diarrhea, nausea, abdominal discomfort, and a metallic taste.
The major benefits of metformin are that it usually does not lead to hypoglycemia when used as monotherapy.
Dosing is typically twice daily; however, it can be dosed three times daily or once daily (extended release). Thiazolidinediones (TZDs) are agonists of peroxisome proliferator-activated receptor gamma (PPARI?) and primarily enhance sensitivity of muscle and fat, and mildly of the liver, to exogenous and endogenous insulin. Major side effects include weight gain, with an increase in subcutaneous adiposity, and fluid retention which typically manifests as peripheral edema, but heart failure has been shown to occur on occasion. Insulin secretagogues stimulate secretion of insulin from the pancreas, thereby decreasing hepatic glucose production and enhancing glucose uptake by muscles and fat. Glinides work in a manner similar to sulfonylureas; however, they have a more-rapid onset of action and a short duration of action, so they are a good option for patients with erratic timing of meals. Alpha glucosidase inhibitors competitively block the enzyme alpha glucosidase in the brush borders of the small intestine, which delays absorption of carbohydrates (absorbed in the mid and distal portions of the small intestine instead). Incretin-based therapies can be used as injections (GLP-1 analogs) or as pills (DPP-4 inhibitors). These medications should not be given to the individuals who have a history of medullary thyroid carcinomas or have multiple endocrine neoplasia syndrome type 2. Exenatide is a synthetic form of exendin 4, hormone found in the saliva of the Gila monster, that mimics glucagon-like peptide type 1 (GLP-1). Due to its delaying effects on gastric emptying, the major side effect is GI complaints such as nausea, vomiting, and diarrhea.
Exenatide is currently also available as once a week injection, supplied as a kit containing the 2 mg of extended release exenatide. Dipeptidyl peptidase 4 (DPP 4) is a cell membrane protein that rapidly degrades GLP-1 and glucose-dependent insulinotropic polypeptide. DPP 4 inhibitors act primarily on postprandial blood glucose levels, but reductions in fasting glycemia are also seen. Pramlintide is a synthetic form of amylin, a hormone secreted by beta-cells that acts to suppress glucagon secretion, slow gastric emptying, and suppress appetite through central pathways.
As with exenatide, the major side effects are GI complaints, especially nausea, and hypoglycemia. Currently in the United States it is approved only as an adjunctive therapy with insulin, but it can be used both T1DM and T2DM. The SGLT-2 inhibitors are the newest group of medications approved for treatment of diabetes mellitus.
At this time canagliflozin and dapagliflozin are only medications in this class approved by the FDA for the treatment of type 2 diabetes. The most common side effects of SGLT-inhibitors are vaginal yeast infections and urinary tract infections. Additional benefits are weight loss (two thirds of weight loss is because of loss of fat tissue and one third is because of loss of water) and drop in the blood pressure. These medications are not indicated in children, in patients with type 1 diabetes, patients with frequent ketones in their blood or urine, severe renal impairment.
Reprinted from Endocrine (Robard L, Braithwaite SS, et al; AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. The basal–bolus regimen involves combining a long-acting agent that is used once or twice daily and provides basal insulin needs and a rapid-acting agent for prandial coverage used with meals. The insulin pump allows use of different basal insulin rates in different periods of the day and administration of the meal bolus as a single discrete bolus or as an extended bolus (square bolus) over a set period of time, which allows a better match between insulin delivery and glucose absorption from the meal in patients with abnormalities of gastric emptying.
In patients with gestational diabetes, insulin therapy is indicated when exercise and nutritional therapy are ineffective in controlling prandial and fasting blood glucose levels. Insulin sensitizers and incretin-based therapy should be used early in the course of the disease.

Multiple daily doses of insulin providing basal, prandial, and supplemental insulin are a mainstay of insulin treatment.
Rodbard HW, Blonde L, Braithwaite SS, et al; AACE Diabetes Mellitus Clinical Practice Guidelines Task Force.
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; The STOP-NIDDM Trial Research Group.
This website for under 18's from Roche Diabetes Care contains some great interactive tools to help you and your family learn more about diabetes and encourage you to get more involved.
Accu-Chek Connect is designed to provide diabetes care information, clinical evidence, case studies and tools to support healthcare professionals make timely and effective therapy decisions, helping patients to become more engaged in their diabetes self-management.
The 3-day fasting, pre-prandial and postprandial SMBG testing plan provided in our tool helps your patients follow the 7-point profile SMBG regimen listed in the IDF guidelines. 15 International Diabetes Federation Clinical Guidelines Taskforce and SMBG International Working Group. This website contains information on products which is targeted to a wide range of audiences and could contain product details or information otherwise not accessible or valid in your country. 4 Relation between PPG control & Achieving A1C Goal Adapted from Monnier L, Lapinski H, Collette C. Every 1% drop in HbA 1c can reduce long-term diabetes complications 43% Lower extremity amputation or fatal peripheral vascular disease 37% Microvascular disease 19% Cataract extraction 14% Myocardial infarction 16% Heart failure 12% Stroke UKPDS: Stratton et al. Hormone BloodTissue Injection site Carrier Protein Carrier Protein Hormone Receptor Mode of Action Use of Serum Carrier Protein (e.g.
Insulin analogues compared Insulin receptor affinity IGF-1R affinity Insulin receptor off rate Metabolic potency Mitogenic potency Human insulin =100 Insulin aspart 92 ± 681 ± 981 ± 8101 ± 258 ± 22 Insulin detemir 18 ± 316 ± 1204 ± 92711 Kurtzhals P, et al. Insulin analogues compared Insulin receptor affinity IGF-1R affinity Insulin receptor off rate Metabolic potency Mitogenic potency Human insulin =100 Insulin aspart 92 ± 681 ± 981 ± 8101 ± 258 ± 22 Insulin lispro 84 ± 6156 ± 16100 ± 1182 ± 366 ± 10 Insulin glargine 86 ± 3641 ± 51152 ± 1360 ± 3783 ± 13 Insulin detemir 18 ± 316 ± 1204 ± 92711 Kurtzhals P, et al. Summary Treatment with basal analogues enables patients to reach HbA 1c target with low rate of hypoglycaemia HbA 1c improves but some patients need more Levemir® + OD is associated with: –reduced hypoglycemia in comparison to NPH, and –reduced weight gain in comparison to any other basal insulin.
It helps patients and physicians assess the effect of food, medications, stress, and activity on blood glucose levels. Those who use basal–bolus regimens should self-monitor before each meal and at bedtime (four times daily).
HbA1c is influenced by rapid red blood cell turnover and blood loss; therefore, anemia and hemoglobinopathies can result in inaccurate values.
Treatment options can be divided into insulin sensitizers, secretagogues, alpha glucosidase inhibitors, incretins, pramlintide, SGLT-2 inhibitors, insulin and insulin analogs.
Its primary mechanism of action is suppression of hepatic glucose output, but it also enhances insulin sensitivity of muscle and fat. It can lead to weight loss, and it has been shown to decrease plasma triglycerides concentration (10%-20%). Main adverse effects include weight gain (about 2 kg upon initiation) and hypoglycemia. They have a lower risk of hypoglycemia than sulfonylureas; they have a similar to lower risk of weight gain with initiation of therapy. This is because increased incidence of the thyroid C-cell tumors have been observed with these medications in the mice and rats. GLP-1 is produced in the small intestine and stimulates insulin secretion and inhibits glucagon secretion and hepatic glucose production in a glucose-dependent manner. Hypoglycemia does not occur when exenatide is used as monotherapy or with metformin, but it does occur when exenatide is combined with a sulfonylurea. If a dose is missed, it should be administered as soon as noticed provided that next dose is scheduled 3 or more days later.
Suppression of DPP 4 leads to higher levels of insulin secretion and suppression of glucagon secretion in a glucose-dependent manner.
Patients can see up to a 50% reduction in their insulin requirements with the addition of pramlintide.
SGLT-2 is a protein acting as sodium-glucose co-transporter in the kidney’s proximal tubules whose main function is reabsorption of the filtered glucose from the urine back into the circulation.
Patients should be advised to expect glucose to be in the urine and if they are using urine glucose strips that they will have a positive reading most of the time. There is no upper limit in dosing for therapeutic effect, so it can be used to bring any HbA1c down to near normal levels. Studies have shown that episodes where the patient required assistance from another due to the hypoglycemia occurred between 1 and 3 per 100,000 patient-years. When initiating therapy with glargine or detemir as the basal insulin, traditionally 50% of the total daily dose is given as basal insulin and the rest as prandial insulin divided equally before meals. Self-monitoring of blood glucose in patients with type 2 diabetes who are not using insulin: a systematic review. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

The role of self-monitoring of blood glucose in the care of people with diabetes: report of a global consensus conference. Meal-related structured self-monitoring of blood glucose: effect on diabetes control in nona€“insulin-treated type 2 diabetic patients. Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomized trial [published online ahead of print June 25, 2007]. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy.
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. The AACE recommendations are almost identical to target values published in the International Diabetes Federation (IDF) Guideline on Self-Monitoring of Blood Glucose in Non-Insulin Treated Type 2 Diabetes15. Please be aware that we do not take any responsibility for accessing such information which may not comply with any valid legal process, regulation, registration or usage in the country of your origin.
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Contributions of fasting and postprandial plasnma glucose increments to the overall diurnal hyper glycemia of Type 2 diabetic patients: variations with increasing levels of HBA(1c). Initially some patients require more frequent monitoring, including both preprandial and postprandial readings. The frequency of testing depends on the clinical situation and the patient’s treatment regimen. Physicians should consider these conditions when there is a discrepancy between HbA1c and SMBG values. It affects primarily fasting glycemia; however, some decreases in postprandial glucose concentrations, especially after the midday meal, can also be seen. Metformin causes a small increase in basal and postprandial lactate concentrations in the blood, leading to potential to produce very rare but life-threatening lactic acidosis (<1 in 100,000). The hypoglycemia episodes can be significant (leading to need for assistance, coma, or seizure) and are seen more often in the elderly. GI complaints, such as bloating, abdominal cramps, flatulence, and diarrhea are the main side effects.
Patients must be warned about this risk and be advised to stop taking these medications and seek medical evaluation if acute abdominal pain develops. So far, there is no increased risk in humans but the above groups of individuals should not use these medications.
Other benefits of insulin include its effects on reducing triglycerides levels and increasing HDL. Meal dose of insulin can be fixed, but it is better to determine the dose based on carbohydrate content of the meal. Hala Aly Gamal El Din Professor Of internal medicine Faculty of Medicine - Cairo University. Patients with gestational diabetes who are taking insulin should monitor their blood glucose three or more times daily. The ADA recommends that patients with stable glycemic control be tested at least twice a year.
The PROactive trial (PROspective pioglitAzone Clinical Trial In macroVascular Events) showed that compared with placebo, pioglitazone does not increase cardiovascular risks. The benefits include a 25% reduction in microvascular complications with or without insulin found by a UKPDS trial. It primarily decreases postprandial blood glucose levels; however, a moderate reduction in fasting blood glucose levels can also be seen. This requires learning carbohydrate counting and knowing the dose of insulin required to cover counted carbohydrates.
Patients should be educated on how to use real-time blood glucose values to adjust their food intake and medical therapy.
Table 1, adapted from the ADA’s 2014 Position Statement on diabetes management, demonstrates that correlation between HbA1c and average blood glucose values.
TZDs have been shown to have an association with an increased risk of fractures, particularly in women.
Its effects and side effects are similar to those of exenatide but it may be slightly more powerful in its actions. Patients with T2DM often require insulin, which can be combined with oral hypoglycemic agents. Pioglitazone use leads to lowering triglycerides, increasing high-density lipoprotein cholesterol (HDL), and increasing the low-density lipoprotein cholesterol (LDL) particle size.

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