Postprandial Leptin Responses After an Oral Fat Tolerance Test: Differences in type 2 diabetes

doi:10.2337/diacare.24.7.1299-a

HOME

HELP

FEEDBACK

SUBSCRIPTIONS

Letters: Observations
Letter

Postprandial Leptin Responses After an Oral Fat Tolerance Test

Differences in type 2 diabetes

Stella Iraklianou, MD¹, Andreas Melidonis, MD, PHD¹, Symeon Tournis, MD¹, Evangellia Konstandelou, PHD², Agathoklis Tsatsoulis, MD, PHD, MRCP³, Moysis Elissaf, MD, PHD, FRSH³ and Dimitrios Sideris, PROFESSOR⁴

¹ Diabetic Centre, Tzanio General Hospital
² Hormonological Laboratory, General Hospital of Piraeus, Piraeus
³ Internal Medicine Department, Medical School, University of Ioannina
⁴ Cardiology Department, Medical School, University of Ioannina, Ioannina, Greece

The finding that circulating leptin concentrations exhibit adiurnal pattern (1,2), with peak nocturnal concentrations upto two times higher than nadir levels, raised the hypothesisthat the evaluation of fasting leptin levels might have underestimatedthe effect of food secretagouges on postpradial leptin regulationand action. This variation in diurnal leptinemia is relatedto insulin excursions in response to meals (2), and shiftingmealtime by 6.5 h without changing the light and sleep cycleswill shift plasma-leptin rhythm by 5–7 h (3). In a recentstudy (4), it was reported that meals with high fat contentresult in the production of lower 24-h leptin concentrationscompared with meals high in carbohydrates, a phenomenon attributedto lower insulin excursions after fatty meals. However, theimpact of reduced insulin sensitivity on short-term leptin productionin response to meals has not been investigated in subjects withsimilar degrees of obesity. We hypothesize that patients withtype 2 diabetes (a well-established insulin-resitant state)show lower postprandial incremental leptin production in responseto an oral fat tolerance test.

A total of 18 type 2 diabetic male patients and 14 control subjectswere matched for age and anthropometric parameters. After a14-h fast, a test meal of 700 kcal/m² (consisting of 4.75 gprotein, 24 g carbohydrates, and 65 g fat) (5) was ingested.Blood samples were drawn at fasting and at 2-, 4-, 6-, and 8-hafter the meal to determine the levels of glucose, total cholesterol,triglycerides, HDL-C, insulin, and leptin.

Triglycerides increased significantly from baseline only indiabetic patients (P = 0.001 vs. P = 0.066, respectively), withpeak concentrations attained at 6-h. Postprandial total cholesterol,LDL cholesterol, and HDL cholesterol levels did not differ significantlybetween groups or from levels at fasting. Insulin levels increasedpostprandially in both groups (P = 0.001 and P = 0.002), withpeak values observed at 2 h. Compared with control subjects,diabetic patients displayed a prolonged insulin response, with4-h values being significantly different from fasting insulinlevels (P = 0.008). Although we could not legitimately evaluatethe significance of differences at each time point (P > 0.05)(Fig. 1), leptin levels tended to decrease postprandially inboth groups, with nadir levels observed at 4 h in diabetic patientsand at 2 h in control subjects. Leptin levels at 4 h were significantlylower in diabetic patients compared with control subjects (4.12± 0.45 vs. 5.85 ± 0.47 ng/ml, P = 0.015).

View larger version (11K):
[in this window]
[in a new window]

Figure 1 — Plasma leptin after ingestion of the test meal. — - —, control subjects (P = 0.332); ——, type 2 diabetic patients (P = 0.698); ¶P = 0.015 for the comparison of leptin levels at 4 h between the two groups.

Although we did not observe significant variations of leptinconcentrations in the two groups, some points need particularconsideration. The initial decrease in leptin concentrationobserved at 2 h was common in both groups. Interestingly, intype 2 diabetic patients, leptin continued to decline contraryto control subjects, with nadir levels observed at 4 h. Regardlessof feeding, this early waning appears to be a continuation ofdecline from peak nocturnal levels. The same tendency was observedin another study (1), where the 24-h profiles of circulatingleptin levels were studied using isocaloric diet. No such decreasewas observed after lunch, supper, or evening snack.

Although there was no interaction between time and postprandialleptin performance, leptin concentrations continued to declineat 4 h in type 2 diabetic patients, reaching values significantlylower compared with those of control subjects, in whom leptintended to increase after the initial drop. A similar time differenceregarding leptin increase was observed during hyperinsulinemicclamp studies, where a significant increase in leptin concentrationwas observed after 6 and 8.5 h in control subjects and type2 diabetic patients, respectively (6). It is reported that aninsulin-mediated increase in leptin levels is dependent on glucoseentry and metabolism in adipocytes (7). We hypothesize thatthe delayed response of leptin observed in diabetic patientsmight be related to impaired-insulin sensitivity at the levelof adipose tissue. Indirect evidence of insulin resistance (8,9)in our study arises from the enhanced triglyceride responseexhibited only by diabetic patients. Although we cannot excludethe contribution of relative insulin deficiency in impairedleptin response found in diabetic patients, the comparable insulinconcentration in the two groups does not favor this hypothesis.

In conclusion, we found that a lipid load does not have a short-termeffect on leptin levels in both type 2 diabetic patients andhealthy control subjects. The tendency of a delayed postprandialleptin response in diabetic subjects might be related to impairedinsulin sensitivity at the level of adipose tissue. Furtherstudies are needed to confirm this observation and to addressthe corresponding metabolic significance.

FOOTNOTES

Address correspondence to Andreas Melidonis, MD, PHD, Vizandiou90, Terpsithea, Glyfada, Athens, Greece. E-mail: tzaniodiabetes{at}yahoo.com.

References

Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF: Nocturnal rise of leptin in lean, obese, and non-insulin dependent diabetes mellitus subjects. J Clin Invest 97:1344–1347, 1996[Medline]
Saad MF, Riad-Gabriel MG, Khan A, Sharma A, Michael R, Jinagouda SD, Boyadjian R, Steil GM: Diurnal and ultradiurnal rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrinol Metab 83:453–459, 1998[Abstract/Free Full Text]
Schoeller DA, Cella LK, Sinha MK, Caro JF: Entrainment of the diurnal rhythm of plasma leptin to meal timing. J Clin Invest 100:1882–1887, 1997[Medline]
Havel PJ, Townsend R, Chaump R, Teff K: High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes 48:334–341, 1999[Abstract]
Patsch JR, Karlin JB, Scott LW, Smith LC, Gotto AM Jr: Inverse relationship between blood levels of high density lipoprotein subfraction 2 and magnitude of postprandial lipemia. Proc Natl Acad Sci U S A 80:1449–1453, 1983[Abstract/Free Full Text]
Malmstrom R, Taskinen MR, Karonen SL, Yki-Jorvinen H: Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM. Diabetologia 39:993–996, 1996[Medline]
Mueller WM, Gregoire F, Stanhope KL, Mobbs CV, Mizuno TM, Warden CH, Stern JS, Havel PJ: Evidence that glucose metabolism regulates leptin secretion from cultured adipocytes. Endocrinology 139:551–558, 1998[Abstract/Free Full Text]
Mekki N, Christofilis MA, Charbonnier M, Atlan-Gepner C, Defroot C, Juhel C, Borel P, Portugal H, Pauli AM, Vialettes B, Lairon D: Influence of obesity and body fat distribution on postprandial lipemia and triglyceride-rich lipoproteins in adult women. J Clin Endocrinol Metabol 84:184–191, 1999[Abstract/Free Full Text]
Ida Chen YD, Swami S, Skowronski R, Coulston A, Reaven GM: Differences in postprandial lipemia between patients with normal glucose tolerance and non insulin-dependent diabetes mellitus. J Clin Endocrinol Metabol 76:172–177, 1997[Abstract]