TABLE 5.
Biochemical measurements obtained from an oral glucose tolerance test in 5,885 non-diabetic or treatment-naïve individuals from the Danish Inter99 study stratified according to 6 MTNR1B genotypes
| N | Age (years) | Plasma glucose (mmol/l) |
Serum insulin (pmol/l) |
Homa-IR | Insulinogenic index | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Fasting | 30 min | 120 min | Fasting | 30 min | 120 min | |||||
| G24E (rs8192552) | ||||||||||
| Wild type | 4,736 | 46 ± 8 | 5.5 ± 0.8 | 8.7 ± 1.9 | 6.2 ± 2.1 | 34 (24–51) | 243 (174–349) | 155 (96–253) | 8.3 (5.6–12.8) | 24.3 (16.8–35.9) |
| Heterozygous | 995 | 46 ± 8 | 5.5 ± 0.6 | 8.7 ± 1.8 | 6.2 ± 2.0 | 35 (24–53) | 263 (181–368) | 160 (95–277) | 8.3 (5.7–13.1) | 25.1 (17.1–38.4) |
| Homozygous | 36 | 45 ± 10 | 5.3 ± 0.8 | 8.1 ± 1.6 | 6.8 ± 2.3 | 38 (24–53) | 257 (1,799–380) | 168 (117–295) | 9.2 (5.4–12.1) | 28.6 (20.5–39.0) |
| Effect size | −0.06 mmol/l | 0.01 mmol/l | 0.04 mmol/l | 1% | 4% | 3% | 0% | 4% | ||
| 95% CI | −0.1 to −0.01 | −0.1 to 0.1 | −0.09 to 0.2 | −3 to 5 | 1 to 8 | −2 to 8 | −4 to 4 | 0 to 8 | ||
| Padd | 0.017* | 0.91 | 0.53 | 0.62 | 0.018 | 0.25 | 0.96 | 0.040 | ||
| L60R | ||||||||||
| Wild type | 5,764 | 46 ± 8 | 5.5 ± 0.8 | 8.7 ± 1.9 | 6.2 ± 2.1 | 34 (24–51) | 244 (175–354) | 156 (96–256) | 8.3 (5.6–12.9) | 24.4 (16.8–36.3) |
| Heterozygous | 4 | 48 ± 9 | 5.6 ± 0.5 | 9.1 ± 1.8 | 5.5 ± 2.6 | 17 (15–21) | 147 (109–173) | 95 (79–122) | 4.2 (3.6–5.3) | 12.1 (9.3–14.3) |
| Effect size | 0.01 mmol/l | 0.3 mmol/l | −0.8 mmol/l | −66% | −67% | −58% | −66% | −83% | ||
| 95% CI | −0.7 to 0.7 | −1.4 to 2.0 | −2.8 to 1.2 | −124 to −9 | −130 to −4 | −136 to 20 | −127 to −4 | −152 to −13 | ||
| Pdom | 0.98 | 0.76 | 0.45 | 0.023 | 0.036 | 0.15 | 0.037 | 0.020* | ||
| V124I | ||||||||||
| Wild type | 5,767 | 46 ± 8 | 5.5 ± 0.8 | 8.7 ± 1.9 | 6.2 ± 2.1 | 34 (24–51) | 245 (175–354) | 156 (96–256) | 8.3 (5.7–12.9) | 24.5 (16.8–36.5) |
| Heterozygous | 41 | 46 ± 8 | 5.6 ± 0.7 | 9.1 ± 1.7 | 6.4 ± 2.6 | 31 (21–44) | 235 (145–321) | 140 (74–234) | 7.7 (5.2–10.6) | 22.9 (15.8–30.9) |
| Effect size | −0.0 mmol/l | 0.4 mmol/l | 0.2 mmol/l | 7% | 14% | 15% | 7% | 13% | ||
| 95% CI | −0.2 to 0.2 | −0.1 to 0.9 | −0.4 to 0.8 | −25 to 11 | −31 to 3 | −39 to 11 | −27 to 12 | −33 to 6 | ||
| Pdom | 0.95 | 0.16 | 0.54 | 0.42 | 0.12 | 0.26 | 0.47 | 0.18 | ||
| R138C (rs61746674) | ||||||||||
| Wild type | 5,781 | 46 ± 8 | 5.5 ± 0.8 | 8.7 ± 1.9 | 6.2 ± 2.1 | 34 (24–51) | 245 (175–353) | 156 (96–256) | 8.3 (5.7–12.9) | 24.5 (16.8–36.4) |
| Heterozygous | 12 | 45 ± 8 | 5.5 ± 0.6 | 8.2 ± 1.7 | 6.1 ± 1.1 | 33 (23–38) | 240 (197–276) | 167 (121–212) | 8.0 (5.2–9.0) | 25.3 (17.8–32.1) |
| Effect size | −0.09 mmol/l | −0.6 mmol/l | −0.1 mmol/l | 22% | 8% | 3% | 23% | 2% | ||
| 95% CI | −0.5 to 0.3 | −1.6 to 0.4 | −1.3 to 1.1 | −55 to 11 | −42 to 27 | −42 to 49 | −59 to 12 | −37 to 40 | ||
| Pdom | 0.69 | 0.26 | 0.86 | 0.19 | 0.66 | 0.88 | 0.20 | 0.92 | ||
| R231H (rs8192553) | ||||||||||
| Wild type | 5,733 | 46 ± 8 | 5.5 ± 0.8 | 8.7 ± 1.9 | 6.2 ± 2.1 | 34 (24–51) | 245 (175–353) | 156 (97–256) | 8.3 (5.7–12.9) | 24.4 (16.8–36.3) |
| Heterozygous | 61 | 47 ± 7 | 5.6 ± 0.9 | 8.8 ± 2.1 | 6.0 ± 2.6 | 37 (27–48) | 294 (202–376) | 151 (63–230) | 8.9 (6.2–12.0) | 29.1 (18.7–39.5) |
| Homozygous | 1 | 55 | 5.2 | 6.9 | 4.2 | 37 | 212 | 65 | 8.6 | 25.4 |
| Effect size | 0.0 mmol/l | 0.0 mmol/l | −0.4 mmol/l | 2% | 9% | 24% | 2% | 3% | ||
| 95% CI | −0.2 to 0.2 | −0.4 to 0.5 | −0.9 to 0.2 | −13 to 18 | −6 to 23 | −44 to −4 | −14 to 19 | −14 to 20 | ||
| Pdom | 1.0 | 0.91 | 0.17 | 0.78 | 0.24 | 0.021* | 0.78 | 0.75 | ||
| K243R (rs61747139) | ||||||||||
| Wild type | 5,418 | 46 ± 8 | 5.5 ± 0.8 | 8.7 ± 1.9 | 6.2 ± 2.1 | 34 (24–51) | 246 (175–353) | 156 (96–256) | 8.3 (5.6–12.9) | 24.5 (16.8–36.3) |
| Heterozygous | 379 | 46 ± 7 | 5.5 ± 0.7 | 8.6 ± 1.8 | 6.1 ± 2.0 | 35 (24–50) | 232 (177–358) | 154 (95–239) | 8.3 (5.7–13.0) | 24.5 (17.3–36.6) |
| Homozygous | 3 | 48 ± 12 | 5.8 ± 1.3 | 9.2 ± 2.4 | 8.5 ± 4.8 | 27 (26–28) | 313 (190–318) | 146 (146–250) | 6.0 (5.8–6.2) | 37.0 (36.0–37.9) |
| Effect size | −0.08 mmol/l | −0.09 mmol/l | −0.1 mmol/l | 1% | 0% | 3% | 0% | 2% | ||
| 95% CI | −0.2 to −0.01 | −0.3 to 0.1 | −0.3 to 0.1 | −5 to 8 | −6 to 6 | −11 to 6 | −7 to 7 | −5 to 9 | ||
| Pdom | 0.035* | 0.32 | 0.24 | 0.66 | 0.95 | 0.51 | 0.98 | 0.57 | ||
Data are means ± SD or median (interquartile range) unless otherwise indicated, stratified according to genotypes of six MTNR1B variants. Values of serum insulin, HOMA-IR, and insulinogenic index were logarithmically transformed before statistical analyses. Effect sizes and P values are calculated assuming an additive (Padd) or dominant (Pdom) genetic model of inheritance adjusted for age and sex.
*Remains significant after adjusting for the difference in BMI. HOMA-IR and insulinogenic index are calculated as described in online-only appendix.