Original Article

Insulin Treatment of Patients with Diabetes and the Problem of Weight Gain: What Do You Need to Know as a Diabetes Nurse Educator?

D Kruger, K Kulkarni

Keywords

diabetes, drug therapy, insulin, nutritional management, patient education, weight loss

Citation

D Kruger, K Kulkarni. Insulin Treatment of Patients with Diabetes and the Problem of Weight Gain: What Do You Need to Know as a Diabetes Nurse Educator?. The Internet Journal of Advanced Nursing Practice. 2006 Volume 9 Number 1.

Abstract

Reducing hyperglycemia through effective diabetes management in patients with type 1 or type 2 diabetes can reduce progression or development of diabetic complications: this article examines the need for effective pharmacological therapy while minimizing the risk of weight gain, and the role of advanced practice nurses (APNs) in helping patients with these issues. Insulin therapy is effective, but its potential side effects, including excessive weight gain, can undermine treatment success through adverse physiological consequences and patient demotivation. Educational and practical steps can be taken and therapy choices made that can limit this problem. APNs, working closely with patients who have diabetes, with diabetes nurse educators and with dietitians, have a role to play in weight management. Education concerning medical nutritional therapy and physical activity contributes to the overall care of the patient and effective self-management of diabetes. APNs need to maintain an awareness of insulin options and of other emerging diabetes therapies.

 

Work performed at:
Henry Ford Medical Center - New Center One
Division of Endocrinology, Diabetes, Bone and Mineral Disorders
Detroit, MI

Funding: The publication of this article has been supported by Novo Nordisk Inc.

The Need for Effective Pharmacological Therapy in Patients with Diabetes

Optimal glycemic control is paramount in the treatment of diabetes. Well-known, large-scale studies such as the Diabetes Control and Complications Trial (DCCT) in patients with type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS) or the Kumamoto study in patients with type 2 diabetes have conclusively shown that elevated levels of blood glucose are associated with the occurrence of microvascular complications, such as retinopathy and neuropathy (1, 2, 3). The DCCT was a prospective trial involving 1441 patients with type 1 diabetes randomized to either an intensive (three to four insulin injections/day or insulin pump) or conventional (one to two insulin injections/day) treatment protocol. Those in the intensive group achieved a better level of glycemic control than those in the conventional group (median HbA1c 7.3% vs. 9.1%, respectively; p < 0.001), and this was associated with a reduction of development or progression of microvascular complications of up to 76% (1). In the Kumamoto trial (2) involving 110 patients with type 2 diabetes, a better level of metabolic control was achieved with intensified insulin treatment (three or more insulin injections: rapid-acting insulin at mealtimes and intermediate-acting insulin at bedtime) compared with conventional treatment (two intermediate-acting insulin injections daily), with respective mean HbA1c values of 7.1% and 9.4% (p < 0.001). This improved control was associated with a reduction in risk for retinopathy of up to 76% over 6 years of treatment.

Data from the DCCT cohort subsequently reported by the DCCT/Epidemiology of Diabetes Interventions and Complications (EDIC) researchers demonstrate that improved control achieved through intensive insulin therapy also has a positive and lasting impact on macrovascular outcomes in diabetes (4). Patients from the original DCCT cohort have been followed up for a mean 17 years, during which time the event rate for nonfatal myocardial infarction (MI), stroke, or death from cardiovascular disease was reduced by 57% (p = 0.02) among patients who received intensive therapy during the DCCT study. This observation was made despite the mean HbA1c values of the two study groups converging after completion of DCCT, as most patients elected to receive intensive therapy. A reduction in macrovascular events with improved glycemic control was also suggested for patients with type 2 diabetes in the UKPDS study, where for each 1% reduction in HbA1c there was a 14% reduction in events such as MI, stroke and amputation (5). An increased risk in cardiovascular mortality and morbidity is also thought to be associated with high glucose levels after eating (6).

The complications of diabetes, such as blindness, kidney failure and MI, contribute considerably to the morbidity and mortality suffered by patients with diabetes, and severely affects their quality of life (7). In order to minimize the development and impact of complications, good glycemic control should be aimed for at all times. Standards of care have been published by the American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation (IDF) recommending glycemic control targets for HbA1c, fasting blood glucose (FBG) and postprandial blood glucose (Table 1). To achieve these targets, the healthcare team must be knowledgeable about a wide range of tools: pharmacological intervention, nutritional and physical activity, together with appropriate education and patient support.

Figure 1
Table 1: Glycemic control targets from the ADA, ACCE, and IDF

Insulin is the cornerstone of treatment in patients with type 1 diabetes, while medical nutritional therapy (MNT), exercise and oral antidiabetic agents are current first-line treatments for patients with type 2 diabetes. However, type 2 diabetes is a progressive disease that ultimately requires insulin treatment in the long term. The clinical trials referred to above have shown that insulin therapy, through reduction of elevated blood glucose levels, can give the best possible prognosis to patients with type 1 or type 2 diabetes. In all instances, patients with the best outcomes regarding the prevention of development or progression of diabetic complications were those in the intensively-treated insulin therapy groups.

Limitations of Insulin Treatment

The benefits of insulin treatment in lowering blood glucose are clear; however, there may be drawbacks with insulin treatment that may influence healthcare providers and patients in their choice of treatment regimens. Two main limitations to insulin therapy exist: the risk for hypoglycemia, and weight gain. Hypoglycemia is a feared side effect of insulin therapy, which can cause symptoms such as confusion, disorientation, sweatiness, or in serious cases, coma, convulsions, or even death. Naturally, patients with diabetes wish to avoid hypoglycemia and the APN as well as the diabetes nurse educator are in a prime position to provide patient education to help them in this goal. A less widely addressed issue is the problem of weight gain with insulin treatment.

Weight Gain is Common with Insulin Therapy

Improved glycemic control with insulin is known to be associated with weight gain (3, 8, 9). In a population-based sample of 405 patients with type 1 diabetes, weight gain was significantly associated with improvements in HbA1c (p < 0.001); the patients with the best improvements in glycemic control gained the most weight (9). This finding is consistent with findings from the DCCT where those patients in the intensively treated insulin group gained more weight (by a mean of 4.75 kg) than those in the conventionally treated group (p < 0.001) (10). In this study, many patients (~30%) receiving intensive insulin therapy experienced major weight gain, with an increase in body mass index (BMI) of more than 5 kg/m 2 (Figure 1).

Figure 2
Figure 1: The percentage of adult men (a) and women (b) with major weight gain (increase in BMI of more than 5 kg/m ) receiving intensive (white bars) or conventional (black bars) insulin therapy in the DCCT. The overall pattern of differences over time was significant ( < 0.01) for both sexes (DCCT 2001). © 2001 of, and reproduced with permission from, 2001, 24: 1711–1721 ().

Similarly, patients with type 2 diabetes treated with insulin in the UKPDS gained a mean 6.5 kg – more than twice the weight gain of those assigned to the conventional (diet and exercise) group (p < 0.001) (Figure 2) (3). Those in the insulin-treated group did achieve a significantly better level of metabolic control: median HbA1c 7.1% vs. 7.9% in the conventional group, p < 0.0001.

Figure 3
Figure 2: Weight gain in patients involved in the UKPDS. © 1998 of, and reproduced with permission from 1998; 352: 837–853 ().

The Reasons for Weight Gain Associated with Insulin Therapy

At the simplest level, weight gain results from an increase in energy intake, or a decrease in energy expenditure, or both. There are several mechanisms by which insulin administration may influence the balance of energy input/output, and glycemic control itself may be one of them, as patients have a higher energy turnover when their diabetes is poorly controlled than when their glycemic control is improved. This mechanism was illustrated in a study by Carlson and Campbell looking at the effects of insulin treatment on weight, where six patients with type 2 diabetes and a mean HbA1c of 12.9% were switched from conventional to intensive insulin therapy (11). The intervention reduced the patients' HbA1c to 9.6%, but their bodyweight increased by 2.6 kg and was associated with a 5% decrease in metabolic rate (11). A certain percentage of calories are lost in the diuresis that occurs secondary to hyperglycemia. However, this diuresis means that patients with poorly controlled diabetes have a net loss of energy as glucose is actively excreted into the urine. Thus, improving metabolic control reduces this glucosuria, so energy is retained. Furthermore, the dehydration caused by hyperglycemia is reduced. The net effect is that weight can be quickly gained when glycemic control is improved due to improved fluid balance and glucose retention (12). Thus, in the study by Carlson and Campbell (11) a calculated 30% of the weight gain could be accounted for by decreased metabolic rate while the remaining 70% was due to the effects of eliminating glucosuria.

Insulin is an anabolic hormone, hence can act in the body to build muscle cells, and this effect could also contribute to the weight gain seen with insulin therapy of diabetes. But insulin also acts upon adipocytes to inhibit lipolysis, thus increases in fat mass can also be expected. Indeed, data from the DCCT suggest that the weight gain associated with intensive insulin therapy is due to increases in both fat-free mass (all portions of body tissues not containing fat) and fat mass (10). Similar results have been reported in type 2 diabetes. For example, a 6-month study assessed body weight and composition changes in 35 patients with type 2 diabetes during their first 6 months of insulin therapy. Glycemic control improved with insulin (HbA1c decreased from 9.66% to 7.26, p < 0.0001), and was associated with a gain of both fat (0.85 kg) and fat-free mass (0.55 kg) (13).

Another effect that insulin may have upon weight is via the brain, as insulin is known to act on pathways that affect appetite. These pathways may be impaired in patients with type 2 diabetes, so potentially insulin cannot regulate food intake in the same way as in individuals without diabetes (14, 15).

Finally, weight gain with insulin therapy may be connected with the treatment of hypoglycemia. Low blood glucose levels can be remedied by ingestion of glucose or food. If patients fear the onset of a hypoglycemic episode they may eat to prevent experiencing the symptoms associated with an event, or if a hypoglycemic event occurs they may over-treat by consuming more carbohydrate calories than necessary. In the DCCT, patients who experienced one or more episodes of severe hypoglycemia gained more weight (6.8 kg, p < 0.001) than patients who did not experience any severe episodes (4.7 kg) (8).

The Problem with Weight Gain with Insulin Therapy

Despite the benefits of improved glycemic control with insulin therapy, weight gain is a serious issue, especially in patients with type 2 diabetes who may already be overweight. A well known fact is that bodyweight and cardiovascular risk are associated (16) and that losing weight improves the cardiovascular risk profile in patients with type 2 diabetes (17). Even in patients with type 1 diabetes, excessive weight gain has been associated with a worsening of cardiovascular risk markers such as blood pressure and total cholesterol (18). Weight gain in children diagnosed with type 1 diabetes is associated with features of type 2 diabetes, such as insulin resistance (19, 20). This observation has contributed to recently articulated concepts such as “double diabetes” (insulin resistance concomitant with immunogenic diabetes) and “the accelerator hypothesis” (weight gain as a causal trigger for type 1 and type 2 diabetes, according to genetic background) (20, 21, 22, 23).

Gaining weight with insulin not only has potential health consequences but is also unwelcome for patients from a psychological point of view. Weight gain can affect self-esteem and prove frustrating for patients who are trying to follow a nutrition plan and exercise programs. Body image is an important consideration for patients, many of whom are aware that their insulin treatment can also be misused in order to control weight. A study into the eating habits and insulin use of 76 adolescents with type 1 diabetes showed that insulin omission in order to prevent weight gain was common in girls (24). Consequently, weight gain with insulin use may be a barrier that can undermine the beneficial effects of improving glycemic control.

The fear of weight gain (along with hypoglycemia) is also a barrier to the initiation of insulin in patients with type 2 diabetes (25). Many studies have recommended that insulin treatment should be initiated early in the course of this disease to achieve the best prognosis (26). However, initiation of insulin is sometimes delayed by physicians, and patients with type 2 diabetes are often reluctant to commence insulin therapy due to a variety of reasons, including concern about weight gain (25).

Overcoming Insulin-Associated Weight Gain

An important issue is that the barrier of weight gain with insulin therapy is overcomed; the APN and diabetes nurse educator can play an instrumental role in this. By entering into discussions with the patients about eating patterns, the concept of weight management can be introduced prior to insulin initiation, and before difficulties with adherence to prescribed insulin therapy becomes an issue. This intervention in itself may help to minimize weight gain with insulin therapy. The APN and diabetes nurse educator also has to reassure the patient about the obvious benefits of insulin therapy when discussing the negative effects of weight gain. Some weight gain may be inevitable and the patient should be encouraged to continue to follow nutritional therapy and physical activity regimens while maintaining glycemic control at levels as near as possible to optimal.

The impact of nurse follow-up with respect to adherence to diabetes regimens has, in fact, been studied in a randomized, controlled trial of 36 patients with insulin-treated diabetes (27). The intervention group was prescribed continuing education and reinforcement of medical nutritional therapy, physical activity recommendations, and frequent self-monitoring of blood glucose levels; this intervention was achieved through nurse telephone calls and patient self-management logs (including a nutrition and physical activity diary reviewed by a dietitian). The patients receiving frequent nurse contact demonstrated a reduction in HbA1c levels from baseline (HbA1c 1.2%, p < 0.05) compared to the control group (no intervention, routine care), which demonstrated an increase in HbA1c of 0.6%, p < 0.05. In the intervention group, a greater increase in the adherence to nutritional recommendations than in the control group was found, demonstrating that nurse intervention can have a positive effect on motivation, disease management and metabolic control.

Furthermore, an audit of 43 prospectively referred, poorly-controlled (HbA1c > 7.5%) insulin-treated patients with diabetes followed for 6 months also showed that intervention by diabetes nurse educators was effective in metabolic control and bodyweight management (28). In those patients who improved their metabolic control (63% of patients achieved a final HbA1c of <7.0% or achieved a reduction in HbA1c of >1.0%), no increase in bodyweight (measured by change in BMI from baseline) occurred and no episodes of severe hypoglycemia were observed. Adherence to nutritional plans was discussed by the nurses with patients and referral to registered dietitians was recommended where necessary. Thus, skilled intervention from the APN and/or diabetes nurse educator can assist the patient minimize weight gain in patients treated with insulin.

The choice of insulin and the regimen used may have an impact on weight management in patients with diabetes. The APN should therefore have a solid understanding of available insulins and insulin regimens to be able to best advise and treat patients. Continuous subcutaneous insulin infusion (CSII) with a rapidly absorbed insulin, or basal-bolus therapy (in which patients take up to six injections each day, using both a long- and short-acting insulin formulation) are regarded as the optimal insulin regimens and are commonly used in patients with type 1 diabetes. Patients with type 2 diabetes who still preserve some capacity for endogenous insulin secretion may administer once- or twice-daily insulin in combination with oral antidiabetic agents. With advancing disease they may also need to progress to basal-bolus regimens or CSII.

In recent years, novel insulin analogs have been developed with improved pharmacological characteristics compared to human insulin formulations (29). For example, the basal insulin analogs, insulin glargine and insulin detemir, have more prolonged and less variable absorption profiles than NPH insulin (30, 31), and are associated clinically with a reduced risk of nocturnal hypoglycemia (32, 33). Insulin detemir has shown particular promise in clinical trials with regard to weight outcomes. When compared to NPH insulin, in trials of both type 1 and type 2 diabetes, insulin detemir has been associated with a reduction in weight gain (mean weight difference, 0.5–1.7 kg in 6–12-month studies) at similar or better levels of glycemic control (34, 35, 36, 37, 38, 39, 40, 41). A study of 475 patients with type 2 diabetes showed that insulin detemir or NPH insulin can be added to oral antidiabetic agents to achieve excellent mean HbA1c levels (6.6% and 6.5%, respectively, NS) (42). However, weight gain with insulin detemir was significantly less than with NPH insulin (1.2 vs. 2.8 kg, p < 0.001).

The oral antidiabetic agent, metformin, is often prescribed for overweight patients with type 2 diabetes, and is commonly used in conjunction with insulin. Metformin helps in reducing insulin resistance and also reduces appetite. In combination with insulin, this agent has been associated with less weight gain than placebo, other agents and insulin monotherapy, while achieving comparable or better glycemic control (43, 44, 45). For example, in the study by Douek and colleagues (43), 183 patients with type 2 diabetes maximally controlled on oral agents were randomized to receive metformin or placebo. Insulin was initiated in both groups according to local practice. Those patients treated with metformin experienced less weight gain (difference 1.5 kg, p = 0.02) and a greater decrease in HbA1c (difference of 0.5%, p = 0.02) than those receiving placebo.

Two novel antihyperglycemic agents that have recently been introduced are also showing promise in regulating weight in patients with diabetes. Exenatide is the first mimetic of the incretin hormone, GLP-I, and its therapeutic actions include glucose-dependent insulin secretion (46) and suppression of inappropriate glucagon secretion in the postprandial period (47). Exenatide is injected subcutaneously and, when used in combination with metformin and/or sulfonylureas in patients with type 2 diabetes, has been found to significantly improve glycemic control compared with placebo (48, 49, 50). In these and other studies, significant weight loss of up to 1.8 kg has been seen with exenatide treatment (48, 50, 51). Exenatide was also associated with favorable weight loss when compared with insulin glargine in a study of 551 patients with type 2 diabetes (52). Both insulin glargine or exenatide added to existing oral therapy improved HbA1c levels by 1.11% from baseline, but patients treated with exenatide lost 2.3 kg in weight, whereas those given insulin glargine gained 1.8 kg (difference, 4.1 kg [CI: 4.6 to 3.5 kg]). However, a significantly higher incidence of gastrointestinal adverse effects in the exenatide group occurred although these effects tend to be transient.

The second novel antihyperglycemic agent is the amylin analog, pramlintide, which is also given by subcutaneous injection. Amylin is a naturally occurring hormone that is co-secreted with insulin from pancreatic beta cells in response to meal stimuli and exerts its antidiabetic effects via suppression of postprandial glucagon secretion and delaying of gastric emptying (53). Endogenous amylin secretion is deficient in patients with type 1 or type 2 diabetes, so pramlintide (amylin analog) can be use to complement insulin treatment (54). Preprandial pramlintide, as an adjunct to insulin, has significantly reduced HbA1c in comparison to placebo in patients with type 1 or type 2 diabetes in studies of up to one year (55, 56, 57). This improvement in glycemic control has also been accompanied by a decrease in bodyweight, of up to 2 kg (55, 56, 57, 58). These novel agents, as well as others in development, appear to present new treatment options for patients with diabetes, especially in those concerned about their weight.

Conclusion

Treatment with insulin of both type 1 and type 2 diabetes has obvious benefits. However, drawbacks to insulin treatment can exist, one being the tendency for patients to gain weight. Consequently, the issue of weight management with insulin therapy is an area that should be addressed by the both the APN and diabetes nurse educator. This important role will involve advising, encouraging and motivating patients with regard to their nutritional therapy and exercise programs. New insulins and other novel antidiabetic agents may also be able to offer fresh therapy options for preventing weight gain in patients with diabetes. Nurses providing patient education need to acquire and maintain a knowledge of these agents so they can advise patients about their use, and recognize opportunities for their introduction into patients' therapeutic and weight management regimens. While weight gain is currently a common and unwelcome aspect of insulin therapy, the problem that must be kept in perspective and that can be mitigated by appropriate interventions.

Conflict of Interest

No inducements have been made by any commercial entity to submit the manuscript for publication.

Acknowledgment

The assistance of Murray Edmunds of Watermeadow Medical in drafting this article is gratefully acknowledged.

Correspondence to

Davida F. Kruger, MSN, APRN,BC, BC-ADM Henry Ford Health System Division of Endocrinology, Diabetes, Bone and Mineral Disorders 3031 West Grand Blvd, Suite 800 Detroit, MI 48202 Tel: 313-916-3906 Fax: 313-916-3907 Email: Dkruger1@hfhs.org

References

1. DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine 1993; 329 (14): 977-986.
2. Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Research and Clinical Practice 1995; 28 (2): 103-117.
3. UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352 (9131): 837-853.
4. DCCT/EDIC Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. New England Journal of Medicine 2005; 353 (25): 2643-2653.
5. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. British Medical Journal 2000; 321 (7258): 405-412.
6. Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, Ziegelasch HJ, Lindner J; DIS Group. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia 1996; 39 (12): 1577-1583.
7. UKPDS Group. Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37). Diabetes Care 1999; 22 (7): 1125-136.
8. DCCT Research Group. Weight gain associated with intensive therapy in the diabetes control and complications trial. Diabetes Care 1988; 11 (7): 567-573.
9. Wing RR, Klein R, Moss SE. Weight gain associated with improved glycemic control in population-based sample of subjects with type I diabetes. Diabetes Care 1990; 13 (11): 1106-1109.
10. DCCT Research Group. Influence of intensive diabetes treatment on bodyweight and composition of adults with type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care 2001; 24 (10): 1711-1721.
11. Carlson MG, Campbell PJ. Intensive insulin therapy and weight gain in IDDM. Diabetes 1993; 42 (12): 1700-1707.
12. Makimattila S, Nikkila K, Yki-Jarvinen H. Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus. Diabetologia 1999; 42 (4): 406-412.
13. Salle A, Guilloteau G, Ryan M, Bouhanick B, Ritz P. Effect of insulin treatment on the body composition of Type 2 diabetic patients. Diabetic Medicine 2004; 21 (12): 1298-1303.
14. Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science 2000; 289 (5487): 2122-2125.
15. Schwartz MW. Enhanced: staying slim with insulin in mind. Science 2000; 289 (5487): 2066-2067.
16. Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. Journal of the American College of Nutrition 2003; 22 (5): 331-339.
17. Markovic TP, Campbell LV, Balasubramanian S, Jenkins AB, Fleury AC, Simons LA, Chisholm DJ. Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes. Diabetes
Care 1998; 21 (5): 695-700.
18. Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. Journal of the American Medical Association 1998; 280 (2): 140-146.
19. Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ. Evidence for heterogeneous pathogenesis of insulin-treated diabetes in black and white children. Diabetes Care 2003; 26 (10): 2876-2882.
20. Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ. Changing prevalence of overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care 2003; 26 (10): 2871-2875.
21. Erbey JR, Kuller LH, Becker DJ, Orchard TJ. The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population. Diabetes Care 1998; 21 (4): 610-614.
22. Kibirige, M, Metcalf, B, Renuka, R, Wilkin, TJ. Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes. Diabetes Care 2003; 26 (10): 2865-2870.
23. Wilkin TJ. Diabetes mellitus: Type 1 or type 2? The accelerator hypothesis. Journal of Pediatrics 2002; 141 (3): 449-450.
24. Bryden KS, Neil A, Mayou RA, Peveler RC, Fairburn CG, Dunger DB. Eating habits, body weight, and insulin misuse. A longitudinal study of teenagers and young adults with type 1 diabetes. Diabetes Care 1999; 22 (12): 1956-1960.
25. Korytkowski, M. When oral agents fail: practical barriers to starting insulin. International Journal of Obesity and Related Metabolic Disorders 2002; 26 (Suppl 3): S18-24.
26. Campbell RK, White JR Jr. Insulin therapy in type 2 diabetes. Journal of the American Pharmaceutical Association (Washington, DC) 2002; 42 (4): 602-611.
27. Kim HS, Oh JA. Adherence to diabetes control recommendations: impact of nurse telephone calls. Journal of Advanced Nursing 2003; 44 (3): 256-261.
28. Yong, A, Power, E, Gill, G. Improving glycaemic control of insulin-treated diabetic patients-a structured audit of specialist nurse intervention. Journal of Clinical Nursing 2002; 11 (6): 773-776.
29. Lindholm, A. New insulins in the treatment of diabetes mellitus. Best Practice Research Clinical Gastroenterology 2002; 16 (3): 475-492.
30. Heise, T, Nosek, L, Ronn, B. B, Endahl, L, Heinemann, L, Kapitza, C, Draeger, E. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes 2004; 53 (6): 1614-1620.
31. Scholtz HE, Pretorius SG, Wessels DH, Becker RH. Pharmacokinetic and glucodynamic variability: assessment of insulin glargine, NPH insulin and insulin ultralente in health volunteers using a euglycaemic clamp technique. Diabetologia 2005; 48 (10): 1988-1995.
32. Chapman TM, Perry CM. Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus. Drugs 2004; 64 (22): 2577-2595.
33. McKeage K, Goa, KL. Spotlight on insulin glargine in type 1 and 2 diabetes mellitus. Treatments in Endocrinology 2002; 1 (1): 55-58.
34. De Leeuw I, Vague P, Selam JL, Skeie S, Lang H, Draeger E, Elte JW. Insulin detemir used in basal-bolus therapy in people with type 1 diabetes is associated with a lower risk of nocturnal hypoglycaemia and less weight gain over 12 months in comparison to NPH insulin. Diabetes Obesity & Metabolism 2005; 7 (1): 73-82.
35. Haak, T, Tiengo, A, Draeger, E, Suntum, M, Waldhausl, W. Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. Diabetes Obesity & Metabolism 2005; 7 (1): 56-64.
36. Home P, Bartley P, Russell-Jones D, Hanaire-Broutin H, Heeg JE, Abrams P, Landin-Olsson M, Hylleberg B, Lang H, Draeger E; Study to Evaluate the Administration of Detemir Insulin Efficacy, Safety and Suitability (STEADINESS) Study Group. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial. Diabetes Care 2004; 27 (5): 1081-1087.
37. Raslova K, Bogoev M, Raz I, Leth G, Gall MA, Hancu N. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Research & Clinical Practice 2004; 66 (2): 193-201.
38. Russell-Jones D, Simpson R, Hylleberg B, Draeger E. Bolinder J. Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen. Clinical Therapeutics 2004; 26 (5): 724-736.
39. Standl E, Lang H, Roberts A. The 12-month efficacy and safety of insulin detemir and NPH insulin in basal-bolus therapy for the treatment of type 1 diabetes. Diabetes Technology & Therapeutics 2004; 6 (5): 579-588.
40. Pieber TR, Draeger E, Kristensen A, Grill V. Comparison of three multiple injection regimens for Type 1 diabetes: morning plus dinner or bedtime administration of insulin detemir vs. morning plus bedtime NPH insulin. Diabetic Medicine 2005; 22 (7): 850-857.
41. Vague P, Selam JL, Skeie S, De Leeuw I, Elte JW, Haahr H, Kristensen A, Draeger E. Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart. Diabetes Care 2003; 26 (3): 590-596.
42. Hermansen K, Derezinski T, Kim H, Gall M-A. Treatment with insulin detemir in combination with oral agents is associated with less risk of hypoglycaemia and less weight gain than NPH insulin at comparable levels of glycaemic improvement in people with Type 2 diabetes. Diabetologia 2004; 47 (Suppl 1): A273.
43. Douek IF, Allen SE, Ewings P, Gale EA, Bingley PJ; for the Metformin Trial Group Continuing metformin when starting insulin in patients with Type 2 diabetes: a double-blind randomized placebo-controlled trial. Diabetic Medicine 2005; 22 (5): 634-640.
44. Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP, Valk GD. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2004; 4: CD003418.
45. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 2005; 65 (3): 385-411.
46. Egan JM, Clocquet AR, Elahi D. The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism 2002; 87 (3): 1282-1290.
47. Nauck M, Meier J. Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regulatory Peptides 2005; 128 (2): 135-148.
48. Buse J, Henry R, Han J, Kim DD, Fineman MS, Baron AD; Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27 (11): 2628-2635.
49. Fineman MS, Bicsak TA, Shen LZ, Taylor K, Gaines E, Varns A, Kim D, Baron AD. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 2003; 26 (8): 2370-2377.
50. Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005; 28 (5): 1083-1091.
51. Poon T, Nelson P, Shen L, Mihm M, Taylor K, Fineman M, Kim D. Exenatide improves glycemic control and reduces body weight in subjects with type 2 diabetes: a dose-ranging study. Diabetes Technology & Therapeutics 2005; 7 (3): 467-477.
52. Heine R, Van Gaal L, Johns D, Mihm MJ, Widel MH, Brodows RG; for GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes. Annals of Internal Medicine 2005; 143 (8): 559-569.
53. Schmitz O, Brock B, Rungby J. Amylin agonists: a novel approach in the treatment of diabetes. Diabetes 2004; 53 (Suppl 3): S233-S238.
54. Kruger DF, Gatcomb PM, Owen SK. Clinical implications of amylin and amylin deficiency. The Diabetes Educator 1999; 25 (3): 389-397.
55. Hollander PA, Levy P, Fineman MS, Maggs DG, Shen LZ, Strobel SA, Weyer C, Kolterman OG. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 2003; 26 (3): 784-790.
56. Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabetic Medicine 2004; 21 (11): 1204-1212.
57. Ratner R, Whitehouse F, Fineman MS, Strobel S, Shen L, Maggs DG, Kolterman OG, Weyer C. Adjunctive therapy with pramlintide lowers HbA1c without concomitant weight gain and increased risk of severe hypoglycemia in patients with type 1 diabetes approaching glycemic targets. Experimental and Clinical Endocrinology Diabetes 2005; 113 (4): 199-204.
58. Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG, Weyer C. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obesity Research 2004; 12 (4): 661-668.

Author Information

Davida F. Kruger, MSN, APRN,BC, BC-ADM
Division of Endocrinology, Diabetes, Bone and Mineral Disorders, Henry Ford Health System

Karmeen Kulkarni, MS, RD, BC-ADM, CDE
Director, Scientific Affairs Abbott Diabetes Care Inc.

Your free access to ISPUB is funded by the following advertisements: