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Diabetologia. 2010 Jan;53(1):36-44. doi: 10.1007/s00125-009-1569-3. Epub 2009 Nov 7.

Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients.

Collaborators (249)

Abrams P, Algoet C, Arnouts P, Ayoubi S, Bachy A, Baeyens J, Balasse E, Bataille G, Beckers D, Beckers V, Becq H, Beirinckx A, Beirinckx J, Bex M, Bocquet A, Bodson A, Bosly F, Bossaert H, Bouillon R, Bouquegneau MS, Bourguignon J, Brussaard H, Buysschaert M, Cardon M, Carlier A, Casteels K, Cavatorta E, Chachati A, Claessens A, Claeys C, Claeys L, Claeys M, Cnop M, Cochez P, Coeckelberghs M, Col V, Colin M, Coolens JL, Coremans P, Corvilain B, Coucke F, Coucke W, Couturier E, Crapé A, Crenier L, Damoiseaux P, Daoudi N, Daper C, Daubresse C, Daubresse JC, De Backer M, De Block C, De Feyter I, De Groot E, De Hauwere R, De Keyser K, De Leeuw I, De Schepper J, De Schynkel K, De Waele K, De Wasch G, Decerf JA, Decochez K, Decraene P, Defoer F, Demaeseneer R, Derdelinckx L, Deweer S, Dooms L, Dorchy H, Driessens S, Du Caju M, Ducobu J, Dumasy V, Duvivier E, Duyck F, Dysseleer A, Emsens L, Engelen W, Ernould C, Ers V, Evenepoel C, Eykens A, Favere N, Fery F, Fils R, Frankart L, Gaham N, Galopin-Vanderstappen E, Garmijn K, Gerard J, Geronooz I, Gillard P, Gillet C, Giri M, Gorus F, Guiot J, Haemers A, Haemers S, Hendrieckx C, Herbaut C, Heremans G, Heureux F, Heyns E, Hilbrands R, Huard A, Hubermont G, Huyghe J, Immegeers V, Jandrain B, Jopart P, Kaufman J, Keymeulen B, Kin-Willems M, Kleynen P, Kockaerts Y, Krzentowski G, Laga K, Lagasse E, Lamberigts G, Lambrecht E, Lebrethon MC, Lefebvre P, Lienart F, Lim Tjin T, Litvine C, Logghe K, Louis J, Maes M, Maes W, Marchal M, Marien P, Massa G, Mathieu C, Mathijs Z, Mattelaer D, Maus Y, Mekeirele K, Merahli F, Mockel J, Monballyu J, Moorkens G, Moureau T, Muls E, Musch W, Nachtegaele P, Naudts K, Neven I, Nicolaij D, Nobels F, Nollet A, Paciorkowski F, Paquot N, Paris I, Peeters C, Peiffer F, Pelckmans MC, Penninckx H, Peters O, Philips JC, Pieron M, Pipeleers D, Platteau K, Poelmans L, Ponchon M, Purnode A, Remy C, Renneboog B, Righes C, Rocour-Brumioul D, Roggemans MP, Rooman R, Rottiers R, Ruige J, Scarniere D, Scheen A, Schils E, Schoemaker I, Schrijvers L, Schuerman M, Schutyser J, Selvais P, Seret N, Spincemaille K, Stassen MP, Strivay M, Struelens M, Taelman P, Tenoutasse S, Terriere L, Teuwen J, Thenaers G, Thiry-Counson G, Tits J, Tsibuabua G, Tsjoen G, Tuyttens C, Unger J, Van Acker K, Van Aken E, Van Aken S, Van Belle P, Van Crombrugge P, Van Den Bruel A, Van Den Saffele J, Van der Auwera B, Van Doorn J, Van Fleteren E, Van Gaal L, Van Garsse L, Van Gijsegem D, Van Helvoirt M, Van Imschoot S, Van Kerchove E, Van Parijs C, Van Pottelbergh I, Van Rooy P, Van Winghem C, Vanbesien J, Vande Mergel X, Vandecauter H, Vandemeulebroucke E, Vandenbroucke M, Vandenbussche E, Vandergheynst A, Vanderijst M, Vanderstappen H, Vanhaverbeke G, Vanneste S, Vannimmen D, Vanuytsel J, Verbiest R, Vercammen C, Vergauwe P, Verhaegen A, Verhaert G, Verjans V, Verniest R, Verschuere J, Vets B, Vieillevoye G, Vinckx J, Vinken S, Warnotte C, Watillon P, Weber E, Weemaes I, Weets I, Winne L.

Author information

1
Diabetes Research Center, Brussels Free University-VUB, 1090 Brussels, Belgium.

Abstract

AIMS/HYPOTHESIS:

The aim of the study was to investigate the use of hyperglycaemic clamp tests to identify individuals who will develop diabetes among insulinoma-associated protein-2 antibody (IA-2A)-positive first-degree relatives (IA-2A(+) FDRs) of type 1 diabetic patients.

METHODS:

Hyperglycaemic clamps were performed in 17 non-diabetic IA-2A(+) FDRs aged 14 to 33 years and in 21 matched healthy volunteers (HVs). Insulin and C-peptide responses were measured during the first (5-10 min) and second (120-150 min) release phase, and after glucagon injection (150-160 min). Clamp-induced C-peptide release was compared with C-peptide release during OGTT.

RESULTS:

Seven (41%) FDRs developed diabetes 3-63 months after their initial clamp test. In all phases they had lower C-peptide responses than non-progressors (p < 0.05) and HVs (p < 0.002). All five FDRs with low first-phase release also had low second-phase release and developed diabetes 3-21 months later. Two of seven FDRs with normal first-phase but low second-phase release developed diabetes after 34 and 63 months, respectively. None of the five FDRs with normal C-peptide responses in all test phases has developed diabetes so far (follow-up 56 to 99 months). OGTT-induced C-peptide release also tended to be lower in progressors than in non-progressors or HVs, but there was less overlap in results between progressors and the other groups using the clamp.

CONCLUSIONS/INTERPRETATION:

Clamp-derived functional variables stratify risk of diabetes in IA-2A(+) FDRs and may more consistently identify progressors than OGTT-derived variables. A low first-phase C-peptide response specifically predicts impending diabetes while a low second-phase response may reflect an earlier disease stage.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00654121

FUNDING:

The insulin trial was financially supported by Novo Nordisk Pharma nv.

PMID:
19898832
DOI:
10.1007/s00125-009-1569-3
[Indexed for MEDLINE]
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