Journal of M ind and M edical Scie nces [600262]

Journal of M ind and M edical Scie nces
Volume 5 |Issue 2 Article 19
2018
Pancreatoge nic t ype 3C di abetes
Anca M ihaela Pantea Stoian
Carol Davila University of M edicine and Ph armacy, N.C. Paulescu National Institute of Di abetes, Nutrition and M etabolic
Dise ase, B ucharest, Romania, ancas toian@yahoo .com
Giorgiana D itu
N.C. Paulescu National Institute of Di abetes, Nutrition and M etabolic Dise ase, B ucharest, Romania
Mircea D iculesc u
Carol Davila University of M edicine and Ph armacy, Bucharest, Romania
Mircea M anuc
Carol Davila University of M edicine and Ph armacy, Bucharest, Romania
Andra Iulia Suceve anu
Emergency Co unty Clinical Hospital of Co nstanta, Romania
See ne xt page for add itional authors
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Pantea Stoian, A nca M ihaela; Ditu , Giorgiana; Dic ulescu, Mircea; M anuc, M ircea; Suceveanu, Andra Iulia; M anuc, D ana; Di aconu,
Camelia C.; Suceveanu, Adr ian Paul; Nitipir, Cornelia; H ainarosie , Razvan; Poiana, Catalina; and S erafinceanu, Cristian (2018)
"Pancreatogenic t ype 3C d iabetes,"Journal of M ind and M edical Scien ces: Vol. 5 : I ss. 2 , A rticle 19.
DOI: 10.22543/7674.52.P270277
Available at:https://s cholar.valpo .edu/jmm s/vol5/iss2/19

Pancreatoge nic t ype 3C di abetes
Cover Page Footn ote
All author s have contributed equal ly to the c ontents of thi s manuscript.
Auth ors
Anca M ihaela Pantea Stoian, G iorgiana Ditu , Mircea Dic ulescu, Mircea M anuc, A ndra Iulia Suceveanu, Dana
Manuc, C amelia C. Diaconu, Adr ian Paul Suceveanu, Cornelia Nitipir, Razvan Hainarosie , Catalina Poiana,
and C ristian Serafinceanu
This research a rticle i s available in J ournal of M ind a nd M edical S ciences:https://s cholar.valpo .edu/jmm s/vol5/iss2/19

J Mind Med Sci. 2018; 5(2): 270-277
doi: 10.22543 /7674.52.P 270277

*Correspond ing author:
Anca Pantea -Stoian, Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania ; E-mail: [anonimizat]

To cite this article : Pantea -Stoian A, Ditu G, Diculescu M, Manuc M, Suceveanu I, Manuc
D, Diaconu C, Suceveanu AP, Nitipir C, Hainarosie R, Poiana C, Serafinceanu C.
Pancreatogenic type 3C diabetes. J Mind Med Sci . 2018; 5(2): 270-277. DOI:
10.22543/7674.52.P 270277

Research article
Pancreatogenic type 3C diabetes
Anca Pantea -Stoian1,2*, Georgiana Ditu2, Mircea Diculescu1, Mircea Manuc1, Andra
Iulia Suceveanu3, Dana Manuc1, Camelia Diaconu1, Adrian Paul Suceveanu3, Cornelia
Nitipir1, Razvan Hainarosie1, Catalina Poiana1, Cristian Serafinceanu1,2
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
2N.C. Paulescu National Institute of Diabetes, Nutrition and Metabolic Diseas e, Bucharest, Romania
3Emergency County Clinical Hospital of Constanta , Romania

Abstract Background . The relationship between chronic pancreatitis and diabetes is well
established. This form of diabetes is secondary to exocrine pancreatic disorder and is
known as diabetes mellitus type 3c (T3cDM).
Materials and Methods . In this retrospective study we included 261 patients, 59
patients being diagnosed with chronic pancreatitis and secondary diabetes mellitus, and
admitted in the Fundeni Clinical Institute, 2nd Department of Gastroenterology or N.C.
Paulescu I nstitute/ Carol Davila University of Medicine and Pharmacy.
Results and Discussions . Patients were 22.2% women and 77.8% men, with an
average age of 56.8 years and 53.4 years respectively. 63% came from urban areas. The
mean duration of chronic pancreatiti s was six years. Non -diabetic patients were
compared with patients who were previously diagnosed with T3cDM and who had been
analyzed for body mass index (BMI). Imaging investigations were also performed to
confirm pseudotumors or pancreatic tumours. Patie nts already considered non -diabetic
had basal blood glucose values and were mostly overweight and obese. In this context,
insulin resistance cannot be excluded for this group of patients.
Conclusions . T3cDM is a new pathological entity that needs to be exp lored more
deeply, and that should benefit from both a diagnostic stratification and treatment.

Keywords  diabetes mellitus, chronic pancreatitis, risk factors, pancreatic surgery, alcohol abuse,
smoking, obesity

Highlights ✓ T3cDM is a new pathological entity that needs to be explored more deeply to lead to
improved diagnosis and therapeutic stability.
✓ More studies are needed on this topic due to the fact that the exact mechanisms of onset
of T3cDM are not fully known.

Anca Pantea -Stoian et al.
271 Introduction
Secondary diabetes is a relatively common entity in
chronic pancreatitis, so named pancreatogenic diabetes
or types 3c diabetes. It is mostly due to changes in
insulin secretion by pancreatic beta cells at islands. As a
rule, the insulin secretory deficit is complete, following
a long evolution of chronic pancreatitis. Beta cell
secretory function decreases relatively parallel to the
decline in pancreatic exocrine function (1). Most
patients with chronic pancreatitis have an exocrine
pancreatic insufficienc y closely correlated with
endocrine function. The prevalence of alteration of
glucose tolerance is 40 -70%, half of these patients
having insulin -susceptible diabetes. Endocrine failure is
progressive and occurs on average ten years after the
diagnosis of c hronic pancreatitis. The severity of
endocrine dysfunction is dependent on the degree of
pancreatic parenchymal involvement, but is also
affected by the level of alcohol consumption. In insulin –
dependent patients who develop secondary diabetes
mellitus of chronic pancreatitis, beta cell function is
somewhat preserved, and glucoregulation is better,
compared to patients with type I diabetes (2, 3).
Data show that T3cDM is commonly associated
with chronic pancreatitis, with a prevalence from 25%
to 80%. A si gnificant risk factor is the duration of
chronic pancreatitis, which also causes the onset of
diabetes due to exhaustion of the pancreatic endocrine
reserve (4, 5).
In the case of hereditary pancreatitis, the mean age
of secondary pancreatitis diabetes is between 38 -53
years, and in the case of chronic pancreatitis for other
causes, the onset age is less specific (6, 7).
Over the past 20 years, significant efforts have been
made both in deciphering the genetic mechanisms that
can compete with chronic pancr eatitis and in the study
of risk factors and/or the progression of this disease (8).
However, the link with T3cDM requires more
systematic investigations to determine the genetic
potential for differentiation between currently known
diabetes, such as type 1 diabetes (T1DM), type 2
diabetes mellitus (T2DM), and latent autoimmune
diabetes of adulthood (LADA), etc. (9).
From an immunological perspective, the
association of T1DM with specific HLA alleles has not
been demonstrated in secondary diabetes of chronic
pancreatitis. This aspect was also able to support the fact
that patients with chronic pancreatitis reach late ( in the
stages of disease evolution) absolute insulin, secondary
diabetes being successfully treated with oral
antidiabetics (10). A small proportion of patients with chronic
pancreatitis and secondary diabetes develop a total
deficiency of endogenous insu lin secretion, but this does
not completely alter the secretion of alpha cells, which
is still minimally preserved. From a pathophysiological
point of view, after an extended period of chronic
pancreatitis evolution, the pancreas loses enough beta
cells so that insulin secretion decreases to complete
deficiency. The small mass of remaining cells no longer
responds to glucose level diffusion perisinusoidal.
Alterations in the enteroinsular axis also correlate with
decreased secretory secretion levels, but di minishing
secreted glucagon levels appear as a consequence of
exocrine dysfunction of alpha cells. Glycemic
contractility is not preserved, hypoglycemia does not
stimulate glucagon secretion, and catecholamine
secretion is maintained in secondary diabetes compared
to T1DM. Hypoglycemia is more severe than in T1DM
due to a lack of glucagon secretion stimulation and
probably also due to associated liver disease,
malnutrition, and alcoholism, all of which are often
associated with chronic pancreatitis (11).
Diagnosis of secondary diabetes by chronic
pancreatitis is based on the determination of pancreatic
C-peptide and apparently concomitantly with the
glycemic profile or the oral glucose tolerance test
(OGTT), along with the determination of glycosylated
hemo globin level (HbA1C%). At the onset of decline in
endocrine function, HbA1C% or peptide C is not helpful
as an assessment criterion.
Determination of post -prandial glycaemia may
provide real benefits in assessing the decline in beta cell
function. For suc h situations, diet, alcohol withdrawal,
and oral antidiabetics offer the main treatment options.
Insulin therapy and basal -bolus enhancement are
indicated for patients with good compliance, and a 7%
HbA1C target is preferred (compared to 6.0%) to avoid
hypoglycemia that may be extremely severe for these
patients. In patients with pancreatogenic diabetes,
ketoacidoses are rare events (12, 13).
The secretion of the pancreatic polypeptide is
absent in the secondary insulin -dependent pancreatitis
due to pancre atic beta cell damage with exocrine
damage. The plasma level of somatostatin secretion is
increased in patients with insulin -requiring diabetes
secondary to chronic pancreatitis (14, 15).
Long -term complications in patients with diabetes
secondary to chron ic pancreatitis compared to those in
T1DM are highly dependent on the duration of diabetes
itself. Life expectancy is generally generally reduced
especially if patients do not give up alcohol and tobacco
(16).

Pancreatogenic type 3C diabetes
272 Materials and Methods
Two hundred and sixty -one patients, women and
men with a chronic history of pancreatitis, who came to
the medical visit for re -evaluation, were investigated.
Other patients who did not have the diagnosis of
pancreatogenic secondary diabetes but who had chronic
pancreatitis were also investigated.
Results
Of the 216 patients diagnosed with chronic
pancreatitis, only 59 (27.3%) cases developed secondary
diabetes, documented prior to the visit. The patients
were 22.2% women and 77.8% men, with average ages
of 56.8 years and 53.4 respectively. 63% came from
urban areas.
The mean duration of chronic pancreatitis was six
years. Non -diabetic patients were compared with
patients who had previously been diagnosed with
diabetes and who were analysed for body mass index
(BMI). Biochemical data and imaging investigations
were performed: abdominal ultrasound, computed
tomography, and nuclear magnetic resonance (Tables 1,
2). We used IBM SPSS 20.0 for statistical analysis Excel
and Epi Info.
Following the analysis of the batches,
• diabetes patients had an average basal blood
sugar of 133 mg / dL [25%, 75%] = [100, 178], the
minimum value was 65 mg / dL, maximum: 396 mg /
dL,
• non-diabetic patients showed the following:
minimum value is 94 mg / dL, maximum: 145 mg / dL,
median: 119 mg / dL, 25% 75% = [105, 144],
• normoponderal nondiabetics: the minimum
value is 62 mg / dl, maximum: 243 mg / dl, median: 110
mg / dl, [25%, 75%] = [95, 135.5] the lowest is 62 mg /
dl, the maximum: 234 mg / dl, the median: 112.5 mg /
dl, [25%, 75%] = 100, 154,
• obese nondiabetics: / dl, median: 115 mg / dl,
[25%, 75%] = [100, 147]).

Figure 1. Basal blood glucose assessment. Basal blood glucose (a jeun) was 133 mg/ dl
(normal <100 mg / dl) in the diabetic and non -diabetic
groups with an average mean value between 110 and
119 mg/ dl, which suggests that basal glycemia is
already being altered in patients who have not been
diagn osed with diabetes secondary to chronic
pancreatitis. Patients diagnosed with secondary diabetes
mellitus with chronic pancreatitis had a mean HbA1c%
of 7.9 and peptide C of 0.7 ng / mL. Reference values
for peptide C were 0.81 -3.85 ng / mL.
Non-diabetic p atients also had altered glycemic
values, requiring additional HbA1C% and C -peptide
tests, possibly performing a glucose tolerance test
(OGTT). The glycemic difference between the two
groups, diabetic vs. non -diabetic, is explained by the fact
that diabeti c patients were already undergoing specific
metformin and basal insulin therapy, and those in the
second batch were found with glycemic values altered
during the re -evaluation visit without having previously
received extensive diabetic investigations or sp ecific
treatment. Differences between batches were significant
(p = 0.0296 Kruskal -Wallis): Diabetics -Nondiabetic –
normoponderal: p value = 0.010725.
Determination of gamma -glutamyl transpeptidase
(GGT) in :
• diabetic patients show a minimum value is 19,
maximum, 2513, median: 128, [25%, 75%] = [97,196];
• underweight nondiabetics: 308, median: 93.5,
[25%, 75%] = [27, 136],
• normoponderal nondiabetics: minimum value
is 15, maximum: 973, median: 92, [25%, 75%] = [68.5,
• overweight: the minimum is 23, max imum:
932, median: 96, [25%, 75%] = [27, 99.5] and obese
nondiabetic patients: = [77,115].
Comparing the values between batches, significant
differences are obtained (0.0000 Kruskall -Wallis):
Diabetic -Nondiabetic normoponderal: p value =
0.000072 and Diab etic-Nondiabetic overweight: p value
= 0.000469 (Figure 2).
GGT catalysis the transfer of the γ -glutamyl group
from peptides such as glutathione (GSH) to other amino
acids. The increase in serum GGT is also due to cell
membrane damage by toxins (including alcohol),
ischemia, infections, or cell membrane disruption of the
enzyme as a result of bile acid action. GGT is an enzyme
specific to the liver and bile ducts. Normal levels in
women are <36 U / L and in men <61 U / L.

Anca Pantea -Stoian et al.
273 . .
Imaging investigations, especially routine
abdominal ultrasound, revealed an incidence of tumours
and pseudotumors in diabetic patients 12/59 (20.3%),
underweight nondiabetics 1/10 (10.00%), normal
nondiabetic 7/84 (8.3%), overweight overdose 1/36
(2.8%), and obese nondiabetics 1/27 (3.7%).
CT scan confirmed these data. Tumour density at
the pancreatic level was the highest in the diabetic
group, 20.3%, reiterating the hypothesis that the
incidence i s higher compared to non -diabetic patients, as
previous research has shown.
By comparing the percentages between diabetics
(20.3%) and overweight nondiabetics (2.8%), p =
0.06354, marginally statistically significant (Figure 3).

Figure 3. Abdominal ultrasonographic evaluation.

Figure 4 . Evaluating ethanol consumption.
Consumption of ethanol for diabetic patients was
52.5% compared to non -diabetic patients 41,4%.
Chronic ethanol consumption is not only a risk factor
that worsens chronic pancreatitis but is also a known risk
factor for chronic liver disease. Chronic pancreatic and
hepatic injury can lead to the installation of caloric
protein malnutrition. Underweight patients with chronic
pancreatitis should therefor e also be investigated from a
nutritional perspective, malnutrition further negatively
affects the prognosis.
The association between alcohol consumption and
sex in the whole sample showed that the proportion of
alcohol -consuming women (27.1%) differed
significantly from the percentage of men consuming
alcohol (70.2%) (p = 0.000001 Chi -square). Smoker
status was described in 18.8% of women and 62.5% of
men (p = 0.000001 Chi -square) (Figure 4).
Figure 2 . GGT assessment by batches.

Pancreatogenic type 3C diabetes
274 Table 1 . Biochemical analyses
Diabetic Nondiabetic
Underweight Nondiabetic
Normal
weight Nondiabetic
Overweight Nondiabetic
Obese p_value
(test)
N 59 (27.3%) 10 (4.6%) 84 (38.9%) 36 (16.7%) 27 (12.5%)
HEMOGLOBIN 13.14 -1.5332 12.99 – 1.6224 13.43 – 1.6989 13.08 – 2.0702 13.58 – 1.7126 0.6247 (ANOVA)
LEUKOCYTE 7500
[5800, 9910] 8015
[7500,12610] 7459
[6265, 8995] 7550
[6585, 8545] 7250
[6000, 9500] 0.5824
(Kruskall -Wallis)
PLATELETS 259640.6 –
98243 274000.0 –
115434 269852.3 –
116441 257916.6 –
112707 259000.0 –
83290 0.9619
(ANOVA)
CALCIUM 8.20
[3.01, 44.50] 9.45
[1.20, 23.00] 7.84
[3.02, 18.45] 8.52
[3.50, 15.05] 4.30
[2.05, 12.70] 0.5527
(Kruskall -Wallis)
FIBRINOGEN 404.0
[342.0, 501.0] 440.0
[257.0, 624.0] 384.2
[317.5, 476.5] 427.5
[364.0, 464.0] 385.0
[319.0, 487.0] 0.7648
(Kruskall -Wallis)
AST 36.0
[26.0, 62.0] 28.5
[17.0, 36.0] 31.0
[23.0, 59,5] 43.0
[26.0, 65.0] 40.0
[26.0, 62.0] 0.1199
(Kruskall -Wallis)
ALT 33.0
[20.0, 59.0] 31.0
[19.0, 34.0] 33.0
[22.0, 47.0] 32.0
[25.0, 50.5] 33.0
[22.0, 57.0] 0.7407
(Kruskall -Wallis)
TOTAL BILIRU –
BIN 36.0
[0.70, 83.00] 0.61
[0.40, 55.00] 27.0
[0.60, 74.00] 37.0
[0.60, 71.50] 41.0
[0.90, 99.00] 0.6031
(Kruskall -Wallis)
GGT 128.0
[97, 196] 93.5
[27, 136] 92
[68.5, 103] 86.5
[72, 99.5] 96
[77, 115] 0.0000
(Kruskall -Wallis)
GLUCOSE 133
[100, 178] 119
[105, 144] 110
[95, 135] 112.5
[100, 154] 115
[100, 147] 0.0296
(Kruskall -Wallis)
LIPASE 143
[91, 243] 232
[123, 300] 133
[95.5, 234] 144
[87, 267] 145
[95, 296] 0.5228
(Kruskall -Wallis)
AMYLASE 100
[71, 145] 111.5
[55, 134] 100
[65, 161] 104.5
[56.5, 156] 85
[65, 156] 0.9953
(Kruskall -Wallis)
Table 2 . Imaging evaluations
Diabetic Nondiabetic
Underweight Nondiabetic
Normal
weight Nondiabetic
Overweight Nondiabetic
Obese p_value
(test)
Number 59 (27.3%) 10 (4.6%) 84 (38.9%) 36 (16.7%) 27 (12.5%)
PANCREATIC Eco
CALCIFICATIONS 33/59 (55.9%) 9/10 (90.0%) 50/84 (59.5%) 23/36 (63.9%) 14/27 (51.9%) 0.2752
(Chi-square)
PANCREATIC Eco
STRUCTURE
Hyperechoic
Hyperechoic +
Heterogeneous
Hypoechogenyc
Hypoechogenyc +
Heterogeneous
Heterogeneous
Normoec hogen

4/59 (6.8%)
3/59 (5.1%)

2/59 (3.4%)
0/59 (0%)

47/59 (79.7%)
3/59 (5.1%)

0/10 (0%)
5/10 (50.0%)

0/10 (0%)
0/10 (0%)

5/10 (50.0%)
0/10 (0%)

3/84 (3.6%)
11/84 (13.1%)

1/84 (1.2%)
1/84 (1.2%)

59/84 (70.2%)
9/84 (10.7%)

2/36 (5.6%)
3/36 (8.3%)

0/36 (0%)
0/36 (0%)

26/36 (72.2%)
5/36 (13.9%)

2/27 (7.4%)
6/27 (22.2%)

0 (0%)
0 (0%)

18/27 (66.7%)
1/27 (5.6%)

0.183328
(Likelihood Rațio)
Eco PANCREATIC
pseudoc yst 20/59 (33.9%) 3/10 (30.0%) 27/84 (32.1%) 19/36 (52.8%) 13/27 (48.1%) 0.175480
(Likelihood Rațio)
Eco_PSEUDO –
TUMOR 12/59 (20.3%) 1/10 (10.0%) 7/84 (8.3%) 1/36 (2.8%) 1/27 (3.7%) 0.037122
(Likelihood Rațio)
Eco_LIPOMA –
THOSIS 13/59 (22.0%) 3/10 (30.0%) 22/84 (26.2%) 11/36 (30.6%) 8/27 (29.6%) 0.891107
(Likelihood Rațio)
Eco_DIMENSI ONS
Atrophyc
Hypertrophic
Hypotrophic
Normal
3/59 (5.1%)
29/59 (49.2%)
7/59 (11.9%)
20/59 (33.9%)
0/10 (0%)
5/10 (50.0%)
2/10 (20.0%)
3/10 (30.0%)
1/84 (1.2%)
40/84 (47.6%)
8/84 (9.5%)
35/84 (41.7%)
0/36 (0%)
20/36 (55.5%)
2/36 (5.6%)
14/36 (38.9%)
1/27 (3.7%)
17/27 (63.0%)
1/27 (3.7%)
8/27 (29.6%)
0.636408
(Likelihood Rațio)

Anca Pantea -Stoian et al.
275
Discussion s
Compared to type I DM, T3cDM shows many
different properties: glycemic lability, more frequent
hypoglycemic episodes, and minimum incidence of
ketoacidosis. The need for insulin administration to
achieve satisfying diabetes mellitus compensation is
significantly lower and response of peripheral tissues to
endogenous and exogenous insulin substantially higher
compared to type I diabetics. These cl inical differences
result from decreased but always preserved insulin
secretion, decreased glucagon production, impaired
external pancreatic secretion, excessive alcohol or
tobacco use, or insufficient or irregular food intake.
Secondary DM in chronic panc reatitis is accompanied
by chronic, microangiopathic, and neuropathic
complications analogous to other DM types (16). Diabetes secondary to pancreatic involvement was
initially described and referred to as pancreatogenic
diabetes. The type IIIC diabetes no menclature was first
proposed in 2014 by the American Diabetes
Association, with the name type 3c diabetes now
commonly accepted (17 -19). The most widely reported
conditions are the presence of chronic pancreatitis
(79%), pancreatic ductal adenocarcinomas (8%),
haemochromatosis (7%), cystic fibrosis (4%), and
previous pancreatic surgery (2%) (20 -22).
As diagnostic criteria, Ewald and Brezel proposed
3 major criteria: documentation of exocrine pancreatic
insufficiency (abnormalities of the pancreas),
documen ted imagistic (ultrasound, CT or MRI), and
absence of markers for T1DM 1 (23). Minor criteria
involve documenting cellular dysfunction (pancreatic
peptide C assay, glycemic profile), insulin resistance, Diabetic Nondiabetic
Underweight Nondiabetic
Normal
weight Nondiabetic
Overweight Nondiabetic
Obese p_value
(test)
Num ber 59 (27.3%) 10 (4.6%) 84 (38.9%) 36 (16.7%) 27 (12.5%)
CT_RMN_SPLENO
MEGAL Y 0 (0%) 0/10 (0%) 2/84 (2.4%) 2/36 (5.6%) 0/27 (0%) 0.240927
(Likelihood Rațio)
CT_RMN
LOCA TION
Caudal
Cephalic
Cephalic -caudal
Cephalic -corporeal
Tail
Body
Corporeal
Corporeo -caudal
Without
2/59 (3.4%)
15/59 (25.4%)
0/59 (0%)
1/59 (1.7%)
1/59 (1.7%)
2/59 (3.4%)
2/59 (3.4%)
3/59 (5.1%)
33/59 (55.9%)
0/10 (0%)
2/10 (20.0%)
0/10 (0%)
2/10 (20.0%)
0/10 (0%)
0/10 (0%)
0/10 (0%)
0/10 (0%)
6/10 (60.0%)
4/84 (4.8%)
17/84 (20.2%)
0/84 (0%)
4/84 (4.8%)
0/84 (0%)
0/84 (0%)
3/84 (3.6%)
4/84 (4.8%)
52/84 (61.9%)
0/36 (0%)
9/36 (25.0%
1/36 (2.8%)
3/36 (8.3%)
2/36 (5.6%)
0/36 (0%)
3/36 (8.3%)
1/36 (2.8%)
17/36 (47.2%)
2/27 (7.4%)
5/27 (18.5%)
0/27 (0%)
4/27 (14.8%)
0/27 (0%)
0/27 (0%)
2/27 (7.4%)
1/27 (3.4%)
13/27 (48.1%)
0,439811
(Likelihood Rațio)
CT_RMN_
NEIGHBORHOOD
STRUCTURES
REPORT
Coledoc
Duodenum
Liver
Spleen
Stomach
Without

3/59 (5.1%)
7/59 (11.9%)
0/59 (0%)
5/59 (8.5%)
3/59 (5.1%)
41/59 (69.5%)

2/10 (20.0%)
1/10 (10.0%)
1/10 (10.0%)
0/10 (0%)
0/10 (0%)
6/10 (60.0%)

5/84 (6.0%)
7/84 (8.3%)
2/84 (2.4%)
4/84 (4.8%)
1/84 (1.2%)
65/84 (77.4%)

5/36 (13.9%)
3/36 (8.3%)
0/36 (0%)
4/36 (11.1%)
4/36 (11.1%)
20/36 (55.6%)

5/27 (18.5%)
3/27 (11.1%)
1/27 (3.7%)
1/27 (3.7%)
2/27 (7.4%)
15/27 (55.6%)
0.193701
(Likelihood Rațio)
PERIPHANTICAL
COLLECTIONS 6/59 (10.2%) 2/10 (20.0%) 12/84 (14.3%) 5/36 (13.9%) 1/27 (3.7%) 0.468933
(Likelihood Rațio)
CALCIFICATIONS 39/59 (66.1%) 7/10 (70.0%) 50/84 (59.5%) 28/36 (77.8%) 16/27 (59.3%) 0.355862
(Likelihood Rațio)
EDS_HTPO 5/59 (8.5%) 1/10 (10.0%) 3/84 (3.6%) 0/36 (0%) 1/27 (3.7%) 0.214733
(Likelihood Rațio)
EDS_
GASTRITIS
ESOPHAGITIS
DUODENITIS
WITHOUT
11/59 (18.6%)
10/59 (16.9%)
12/59 (20.3%)
26/59 (44.1%)
1/10 (10.0%)
2/10 (20.0%)
1/10 (10.0%)
6/10 (60.0%)
11/84 (13.1%)
16/84 (19.0%)
14/84 (16.7%)
43/84 (51.2%)
8/36 (22.2%)
4/36 (11.1%)
5/36 (13.9%)
19/39 (52.8%)
5/27 (18.5%)
3/27 (11.1%)
8/27 (29.6%)
11/84 (40.7%) 0.840650
(Likelihood Rațio)
EDS_ULCER 7/59 (11.9%) 0/10 (0%) 5/84 (6.0%) 5/36 (13.9%) 3/27 (11.1%) 0.338545
(Likelihood Rațio)
HGTH 6/59 (10.2%) 4/10 (40.0%) 21/84 (25.0%) 7/36 (19.4%) 4/27 (14.8%) 0.0930 (Chi-
square)
ESOPHAGEAL
VARICOSE VEINS 5/59 (8.5%) 1/10 (10.0%) 3/84 (3.6%) 1/36 (2.8%) 1/27 (3.7%) 0.625388
(Likelihood Rațio)

Pancreatogenic type 3C diabetes
276 alteration of secretory secretion (glucagon -like pept ide-
1 [GLP -1] and/ or pancreatic polypeptides), and
evaluation of liposoluble vitamin deficiency (A, D, E,
K). Although the duration of chronic pancreatitis
somewhat influences these criteria, the clear
differentiation between T1DM, T2DM and
pancreatogenic type 3C diabetes shows an imprecise
standardization of β -cell dysfunction and insulin
resistance. The lack of the concrete data on glucose
homeostasis in T3cDM makes some interpretations
difficult, so there are still many limitations in this regard,
namel y there are still no precise data that can standardize
both diagnosis and therapeutic options (and that is why
more studies would be necessary. However, with the
little information available thus far, we can conclude
that T3cDM is an important pathological entity, most of
the time underestimated and clinically ignored, initially
treated as a T2DM that evolves into insulin -deficiency,
specific to T1DM. Consistent with other studies, it is
essential to create management strategies for T3cDM,
which must includ e therapeutic options for improving
intestinal absorption, assessing nutritional status, and
minimizing malnutrition. As our study has shown, a
small percentage of patients with chronic pancreatitis
(27.3%) developed T3cDM, the rest requiring
investigation s to confirm or nullify the diagnosis. The
non-diabetic patients, who had changed basal blood
glucose values, were mostly overweight and obese, and
therefore cannot be ruled out in this context of insulin
resistance. This situation should be investigated b y
laboratory tests (peptide C determination, OGTT test)
which for objective reasons could not be achieved in this
study. Patients predisposed to T3cDM are mostly men
with a history of chronic alcohol and tobacco use, again,
consistent with other research s tudies. Imaging
evaluations have detected some abnormalities of the
pancreas, from various degrees of a tumour or
pseudotumor to more complicated clinical situations
requiring surgery and even pancreatectomy (24). While
any patient with chronic pancreatiti s should be
monitored for the development of diabetes, those with
long-standing duration of the disease, prior partial
pancreatectomy, and early onset of calcific disease may
be at higher risk. Those patients developing DM are
likely to have co -existing pa ncreatic exocrine
insufficiency. The treatment administered on one hand,
and the enzymatic insufficiency instituted following
chronic pancreatitis on the other hand, contribute to the
disease expression and evolution (21). The major risks
in all these circ umstances are those of severe
hypoglycemia characteristic of T3cDM. Optimization of lifestyle, nutritional intervention, and education of the
patient with T3cDM did not differ from that of patients
with type 2 diabetes (22, 23).
The major drawback of our study is that we initially
intended to assess the evolution of chronic pancreatitis
and glycemic values in patients previously diagnosed
with pancreatogenic diabetes mellitus. However, we
were unable to continue observations on no n-diabetic
patients, although they were detected in the course of the
hospital visit through basal blood glucose changes. A
second limitation stemmed from lack of availability of
patients, access to more complex determinations in the
diagnosis of pancreati c T3cDM diabetes, and the
assessment of glycemic variability utilizing modern
monitoring devices (continuous blood glucose
monitoring systems).
Conclusions
In light of prior research, together with our results,
we can conclude that T3cDM is a new patholog ical
entity that needs to be explored more deeply to lead to
improved diagnosis and therapeutic stability. More
studies are needed in this regard, from both
epidemiological and pathophysiological perspectives, as
no conclusive data exist in present regardi ng the
population and pathophysiological incidence (due to the
fact that the exact mechanisms of onset of T3cDM are
not fully known).
Conflict of interest disclosure
The authors declare that there are no conflicts of
interest to be disclosed for this article.
Acknowledgment s
All authors have contributed equally to the content
of this manuscript .
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