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Diabetes Care 28:2589-2590, 2005
© 2005 by the American Diabetes Association, Inc.

Letters: Observations

Determinants of Response to Insulin Therapy Following Failure of Oral Agents in Type 2 Diabetes

Janaka Karalliedde, MRCP, Andy Smith, MRCP and Giancarlo Viberti, MD, FRCP

Department of Endocrinology, Diabetes and Internal Medicine, King's College London, Guy's Hospital, London, U.K

Address correspondence to Dr. J. Karalliedde, Department of Endocrinology, Diabetes and Internal Medicine, King's College London, 5th Floor Thomas Guy House, Guy's Hospital, London SE1 9RT, U.K. E-mail: j.karalliedde{at}kcl.ac.uk

Obesity, ethnicity, and concomitant metformin therapy may modify the metabolic response to insulin in patients with type 2 diabetes (1–3). We performed a retrospective case note analysis of 280 type 2 diabetic patients who had failed oral drug therapy, defined as HbA1c (A1C) >7.5% for at least 6 months despite maximum doses of sulfonylurea and metformin, and received treatment with exogenous insulin for at least 12 months for indications other than pregnancy, acute coronary syndrome, stroke, sepsis, or renal failure. Main outcome measures were A1C, body weight, and daily insulin dose. For the purpose of analysis, patients with BMI below and above the median for the whole cohort (28.2 kg/m2) were termed nonobese and obese, respectively. Following 12 months of insulin, overall mean (95% CI) A1C fell 2.2% (1.9–2.6), and weight gain increased by 6.0 kg (5.4–6.6). A1C reduction was similar in both the obese and nonobese groups. Concomitant metformin ameliorated weight gain in the nonobese patients (5.1 [3.8–6.4] vs. 7.4 kg [6.4–8.4], P < 0.01) and reduced daily insulin requirements in the obese (0.59 [0.53–0.65] vs. 0.77 units · kg–1 · day–1 [0.69–0.85], P < 0.001) for equivalent reductions in A1C.

Africans and Caribbeans benefited from a greater reduction in A1C (2.7% [2.2–3.2]) than Caucasians (2.1% [1.8–2.4]) and Asians (1.6% [1.3–2.0]) (P < 0.01) despite smaller insulin requirements (African/Caribbeans 0.53 [0.48–0.57], Caucasians 0.64 [0.60–0.69], and Asians 0.67 units · kg–1 · day–1 [0.56–0.77], P = 0.007). Concomitant metformin use was similar across all ethnic groups. Weight gain was greater in African/Caribbeans (7.1 [6.2–8.0]) than Caucasians (5.6 [4.7–6.4]) and Asians (4.8 kg [3.3–6.4], P < 0.01. Our observation, at variance with a previous study (1), indicates that baseline BMI does not affect the benefit of insulin treatment on metabolic control in type 2 diabetic patients but that obese type 2 diabetic patients require more insulin to overcome their greater insulin resistance. Weight gain is virtually an obligate consequence of insulin therapy–induced glycemic improvement in patients who have failed oral agents, but this is modulated by concomitant metformin treatment, degree of obesity, and ethnicity. Moreover, metformin reduced the requirement of insulin in obese type 2 diabetic patients for equivalent glycemic amelioration, an effect that may mitigate further weight gain.

References

  1. Yki-Jarvinen H, Ryysy L, Kauppila M, Kujansuu E, Lahti J, Marjanen T, Rajala S, Salo S, Seppala P, Tulokas T, Viikari J, Taskinen MR: Effect of obesity on response to insulin therapy in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82:4037–4043, 1997[Abstract/Free Full Text]
  2. Argawal L, Emanuele NV, Abraira C, Henderson WG, Levin SR, Sawin CT, Silbert CK, Nuttall FQ, Comstock JP, Colwel JA: Ethnic differences in the glycemic response to exogenous insulin treatment in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM). Diabetes Care 21:510–515, 1998[Abstract]
  3. Aviles-Santa L, Sinding J, Raskin P: Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 131:182–188, 1999[Abstract/Free Full Text]

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