Supplemental Material Table S1. Clinical, laboratory ...

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Feb 20, 2011 - Clinical, laboratory and genetic characteristics of MODY probands ... follow-up. Microvascular complications. GCK-1 c.483+2T>Cg. 5/9. Low.
Supplemental Material Table S1. Clinical, laboratory and genetic characteristics of MODY probands

Proband

Variant

GCK-1 GCK-2

c.483+2T>Cg p.Phe423Tyrh

Age at diagnosis of diabetes or MFHa/age at genetic testing (years) 5/9 9/12

GCK-3

p.Arg191Trpg

32/33

Normal

1/NA/NA

6/10

Low

2/2/1

Diet Metformin DPP-4 inhibitor Diet

2/4

Overweight

3/NA/NA

Sulfonylurea

Diet

126–137

6.4–6.6

0.6

No

14/27 1/18 4/8 6/7 12/16 9/12 4/7 30/49 16/19 4/42 5/9 11/15 14/18 3/11 4/11 11/14

Low Normal Normal Normal Normal Low Normal Normal Normal Low Overweight Normal Normal Overweight Normal Normal

2/20/11 3/NA/NA 0/2/0 2/2/1 2/NA/NA 2/3/2 3/7/4 2/3/2 2/1/1 2/2/1 2/3/2 2/2/1 1/2/0 3/6/3 1/2/1 2/2/1

Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet Diet

Diet NA Diet Diet Diet NA NA Metformin* NA Diet NA NA Diet Diet NA Diet

98–124 124–136 109–130 110–114 112–120 109–110 118–123 102–134 115–134 110–120 99–117 112–128 110–122 108–117 124–136 110–121

5.9–6.6 6.9–7.2 5.7–7.1 6.0–6.1 5.6–6.6 5.9–6.5 6.5–6.9 6.5–6.9 6.4–7.0 6.4–6.8 5.8–6.6 6.0–6.8 6.2–6.4 5.9–6.3 6.5–6.8 6.1–6.4

1.2 2.3 0.7 1.2 1.6 0.8 2.1 1.6 2.5 1.6 1.0 2.4 2.1 1.1 1.4 3.2

No NA No No NA NA No No No No NA No NA NA No NA

3/5

Normal

2/NA/NA

Diet

Diet

108–123

6.3–6.3

1.1

No

22/28 8/10

Normal Overweight

3/NA/NA 2/1/1

Diet Diet

129–130 114–130

6.1–NA 6.2–7.1

1.5 1.4

No NA

8/11

Low

2/5/1

Diet Diet DPP-4 inhibitor

NA

106–152

6.1–6.4

0.8

No

1/10

Normal

3/3/2

Sulfonylurea

NA

102–144

5.9–6.8

1.7

No

10/11 7/13

Overweight Normal

2/1/0 2/4/2

Metformin Diet

Diet NA

122–NA 110–118

6.0–NA 5.9–6.1

1.9 2.1

No No

GCK-4

i

GCK-23 GCK-24

c.580-3C>A c.[1135_1154del; 1134_1135ins9]g p.Arg191Trpg p.His416Profs*15g p.Ile110Serfs*6g p.Gln138Proh p.Phe423Tyrh p.Gly264Asph p.Glu221Lysh p.Glu256Alah p.Met37Thri p.Lys169Glui p.Thr255Ileh p.Gly72Argg p.Thr206Metg p.Lys140Gluh p.Ala384Valh p.Arg447Glnh c.[1135_1154del; 1134_1135ins9]g p.Ala188Thrg p.Asp409Valfs*22g

GCK-25

p.Val253Pheh

GCK-5 GCK-6 GCK-7 GCK-8 GCK-9 GCK-10 GCK-11 GCK-12 GCK-13 GCK-14 GCK-15 GCK-16 GCK-17 GCK-18 GCK-19 GCK-20 GCK-21 GCK-22

GCK-26 GCK-27 GCK-28

c.[1135_1154del; 1134_1135ins9]g p.Cys371Serfs*33g p.Arg250Hisi

Referred weight at diagnosisb

Family history of diabetes/MFH (G/S/HT)c

Low Normal

2/2/0 1/2/1

Range of FPGd (mg/dL) follow-up

Range of A1ce (%) follow-up

C-peptidef (ng/mL) follow-up

Microvascular complications

Diet Diet NA

95–116 101–121

6.2–6.7 6.0–6.3

1.2 1.0

NA No

113–126

6.7–7.0

NA

No

Diet

125–138

6.3–6.7

1.8

NA

Treatment at diagnosis

Current treatment

Proband

Variant

GCK-29 GCK-30

p.Thr255Ileh p.Met224Thri

Age at diagnosis of diabetes or MFHa/age at genetic testing (years) 7/7 14/36

Referred weight at diagnosisb

Family history of diabetes/MFH (G/S/HT)c

Treatment at diagnosis

Current treatment

Range of FPGd (mg/dL) follow-up

Range of A1ce (%) follow-up

C-peptidef (ng/mL) follow-up

Normal Normal

3/NA/NA 1/NA/NA

Diet Metformin

Diet Metformin*

109–122 112–149

6.4–6.8 6.4–7.1

0.9 3.6

Microvascular complications

No No Retinopathy; HNF1A-1 p.Ser594Ileh 30/48 Overweight 2/6/2 Insulin OHAs 287–349 10.3–11.7 1.4 Neuropathy; Microalbuminuria HNF1A-2 p.Pro379Thrg 21/47 Normal 2/NA/NA Sulfonylurea NA 70–200 6.8–9.2 0.4 No HNF1A-3 p.Gly292Argfs*25g 12/36 Low 2/NA/NA Sulfonylurea OHAs 80–157 5.8–9.2 1.5 No HNF1A-4 stopcodon lostg 21/34 Normal 2/2/1 Metformin OHAs 156–182 7.4–7.7 2.1 No HNF1A-5 p.Gly292Argfs*25g 18/28 Normal 1/1/0 Insulin Sulfonylurea 96–150 5.6–6.2 1.8 NA HNF1A-6 p.Gly292Argfs*25g 27/30 Normal 2/1/0 Sulfonylurea Sulfonylurea 96–107 5.8–6.0 1.4 No HNF1A-7 p.Pro112Leug 12/14 Normal 1/NA/NA Sulfonylurea NA 93–150 6.2–7.3 1.3 NA HNF1A-8 p.Arg171Terg 16/23 Low 2/NA/NA Metformin Sulfonylurea 105–141 6.5–7.1 3.0 No HNF1A-9 p.Gln520Terg 14/20 Normal 2/7/4 Sulfonylurea Sulfonylurea 88–101 5.2–6.3 2.2 No HNF1A-10 p.Gly292Argfs*25g 27/30 Normal 3/NA/NA Insulin Sulfonylurea 78–167 5.9–6.3 3.2 No a MFH: mild fasting hyperglycemia; b Reported by the patient (“referred weight”); c Familial history - G: generations, S: patients screened, HT: heterozygous patients for the family variant; d FPG: fasting plasma glucose; e A1c: Glycated hemoglobin; f Fasting C-peptide: three years after diagnosis; ACMG five-tier system: g P (Pathogenic), h L.P (Likely pathogenic), i U.S (Uncertain significance); NA: not available; OHAs: more than one oral hypoglycemic agent (other than sulfonylurea) *Metformin was added or maintained in some GCK-MODY patients that were overweighed or gained weight during follow up Normal range: FPG (70 - 99 mg/dL); A1c (4.1 - 6.0 %) and Fasting C-peptide (1.1 – 4.4 ng/mL)