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Dia Care 1981 Welborn 616 9
Dia Care 1981 Welborn 616 9
U n t r y
(M13, F6)
survey
Country
survey
Serum C-peptide
class
low (0. 16 nmol/L)
high (>0. 16 nmol/L)
low (<0.16 nmol/L)
high (>0.16 nmol/L)
Plasma glucose
(mmol/L)
(mean SEM)
12.6 1.3
11.1 0.4
10.1 1.3
9.1 0.6
Correlation coefficient:
serum C-peptide vs.
plasma glucose
-0.14 (NS)
+0.13 (NS)
-0.30 (NS)
+0.20 (NS)
BMI
(mean :
Males
23.3 0.9
27.5 0.5
24.2 0.8
29.3 0.8
t SEM)
Females
23.3 0.8
26.4 1.1
24.4 1.3
28.3 0.7
Correlation coefficient:
serum C-peptide
vs. BMI
+0.34 (NS)
+0.38 (P < 0.001)
+0.03 (NS)
+0.40 (P < 0.001)
NS = not significant.
Thus, using a basal serum C-peptide level of 0.16 nmol/L
as the cutoff point, our diabetic patients were divided into
two groups: one characterized by exclusive insulin require-
ment, lean body mass, and young age of onset and the other
by a high proportion on diet or oral therapy, tendency to
obesity, and age of onset beyond 40 yr.
The 11 subjects with basal C-peptide values in the range
0.17-0.32 nmol/L represent an indeterminate group. Eight
are on insulin, but five on insulin and three on diet or oral
therapy had onset of diabetes over 40 yr. The BMI values
tend to be intermediate (five men BMI 26.0 1.4; six
women BMI 24.6 2. 14, mean SEM).
The influence of duration of known diabetes on mean
serum C-peptide levels is shown in Table 3. Subjects with
longer duration of known diabetes show lower mean C-pep-
tide levels due to an increasing proportion having very low
levels ( ^ 0.02 nmol/L) at the limit of the assay's sensitivity.
With duration under 5 yr, 20% had serum C-peptide < 0.02
nmol/L compared with 63% at 5- 9 yr duration, and 78% at
10 yr duration or more (X
2
= 12.5, P < 0.01). In the dia-
betic patients with high serum C-peptide, duration of known
disease has no obvious influence on the fasting/postprandial
C-peptide levels. Although the proportion of subjects on in-
sulin therapy increases with duration, there is no evidence
for any substantial deterioration in beta-cell function as mea-
sured by the basal serum C-peptide levels.
DISCUSSION
B
imodality of serum C-peptide levels in these two
diverse diabetic populations suggested the feasibil-
ity of discriminating insulin-deficient from insulin-
resistant individuals by a single test. Using a serum
C-peptide level of 0.16 nmol/L as the cutoff point, the two
groups of diabetes segregated were the low serum C-peptide
group showing clinical characteristics of type I diabetes and
the high serum C-peptide group resembling type II diabetes.
The cutoff point selected provides high specificity for insulin
requirement, but further studies are necessary to determine
the clinical category of patients with borderline serum C-
peptide values of 0.17-0.32 nmol/L. The latter may repre-
sent predominantly lean NIDD patients taking insulin, but
TABLE 2
Mean body mass index (BMI) of diabetic patients with low (^0. 16 nmol/L) and high ( >0. l 6 nmol/L) serum C-peptide levels, by age of onset and
treatment category
<0. l 6 nmol/L
BMI, mean SEM
(no. of subjects in parentheses)
> 0.16 nmol/L
Serum C-peptide Males Females Males Females
1. Diabetes onset
S 40 yr
Insulin therapy
Diet/oral therapy
2. Diabetes onset
> 40 yr
Insulin therapy
Diet/oral therapy
23.6 0.7(20)
24.9 1.8(5)
23.2 0.7(15)
24.4 1.9(8)
27.1 2.1(7)
27.6 1.6(11)
27.9 1.1(15)
28.6 0.6(48)
28.5 3.9(5)
28.7 2.5(6)
27.4 1.4(20)
27.3 0.8(43)
618 DIABETES CARE, VOL. 4 NO. 6, NOVEMBER-DECEMBER 1981
BASAL C-PEPT1DE IN TYPE I AND TYPE II DIABETES/T. A. WELBORN, P. GARCIA-WEBB, AND A. M. BONSER
TABLE 3
Mean serum C-peptide values in diabetic patients with low and high levels, classified by duration of diabetes and by treatment categories
Serum C-peptide, mean SEM
(no. of subjects in parentheses)
Duration of diabetes <5 yr 5-9 yr >10yr
1. Diabetic patients with low (:0.16 nmol/L) serum C-peptide
Insulin therapy
2. Diabetic patients with high (>0.16 nmol/L) serum C-peptide
Insulin therapy
Diet/oral therapy
0.09 0.01(15)
0.83 0.14(18)
0.91 0.06(64)
0.05 0.02(8)
0.59 0.08(10)
1.05 0.13(23)
0.03 0.00(23)
0.79 0.08(19)
1.02 0.13(21)
could contain subjects with IDDM progressing to frank insu-
lin deficiency. We have not encountered any diabetic pa-
tients with fasting C-peptide levels in this range who fail to
show a substantial (50% or more) increment in C-peptide
levels after glucagon stimulation. Thus, the possibility of cir-
culating proinsulin, free or antibody-bound, causing spurious
elevation of apparent C-peptide levels seems, remote.
Although the results obtained from fasting compared with
late postprandial serum C-peptide levels were very similar,
sampling after an overnight fast is preferred for purposes of
standardization. The lack of correlation found between
serum C-peptide and plasma glucose levels indicates that
measurement of plasma glucose is not important in interpret-
ing C-peptide status in frank diabetes. We have confirmed
this in further studies using glucagon stimulation. It is con-
ceivable that a well-controlled patient on insulin may com-
pletely suppress C-peptide production, but we have found no
evidence for this phenomenon in a large series of glucagon
stimulation tests.
In epidemiologic studies, the measurement of fasting C-
peptide levels should provide useful data in classifying diabe-
tes, and may prove to be the method of choice. HLA typing
is not specific for type I diabetes, in that many normal indi-
viduals show the diabetic haplotypes. Islet cell antibodies are
present in some patients presenting with type I diabetes
8
but
do not persist.
In the clinical situation, there is often difficulty in allocat-
ing a diabetic patient on insulin therapy to the type I or type
II category, since ketosis proneness is not always evident,
and the absolute need for insulin can only be demonstrated
by withdrawing it under close supervision, generally in hos-
pital. Measurement of the fasting C-peptide levels allows in-
creased confidence in identifying the insulin-dependent ver-
sus the non-insulin-dependent patient.
Duration of diabetes influences C-peptide levels in IDDM,
and as our findings also suggest, in many subjects there is a
progressive disappearance of residual beta-cell function.
9
*
10
Less is known about the influence of duration of diabetes in
NIDDM. Our data show persistence of high levels of basal
serum C-peptide in NIDDM of long duration and suggest
that no substantial wasting or "fallout" of beta-cells occurs,
even in those subjects requiring insulin therapy. Thus, the
assay of basal serum C-peptide levels is especially useful in
classifying the type of diabetes in patients who have been
taking insulin for many years.
ACKNOWLEDGMENTS: The authors gratefully acknowledge the
generous support of Novo Laboratories Pty. Ltd., the Dia-
betes Research Foundation of Western Australia, and the
Lions Save Sight Foundation. We also thank Sister Annette
Morris and Sister Moira Shirley for their excellent technical
assistance.
From the Department of Endocrinoloy and Diabetes, and the
Department of Clinical Biochemistry, Sir Charles Gairdner Hos-
pital, Nedlands, Western Australia.
Address reprint requests to T. A. Welborn, Sir Charles
Gairdner Hospital, The Queen Elizabeth II Medical Centre, Ned-
lands, Western Australia 6009.
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2
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DIABETES CARE, VOL. 4 NO. 6, NOVEMBER-DECEMBER 1981 619