ARTUR CHWALBA, EWA OTTO-BUCZKOWSKA

TYPE LADA (LATENT AUTOIMMUNOLOGICAL

DIABETES IN ADULTS) AS IMPORTANT DIAGNOSTIC
PROBLEM INGENERAL MEDICAL PRACTICE;
CASEPRESENTATION
CUKRZYCA LADA (LATENT AUTOIMMUNOLOGICAL DIABETES IN ADULTS) JAKO WANY, DIAGNOSTYCZNY
PROBLEM W PRAKTYCE PODSTAWOWEJ OPIEKI ZDROWOTNEJ; OPISPRZYPADKW
Medical Specialist Centre of the Silesian Foundation of Children and Youth, with Diabetes, Gliwice, Poland.
Specjalistyczne Centrum Medyczne lskiej Fundacji Dzieci i Modziey z Cukrzyc, Gliwice, Polska.

SUMMARY. Type LADA diabetes is aform of autoimmune-mediated diabetes in adults. From pathophysiological perspective, it is closely related
totype 1 DM, and some authors have even used the term type 1.5 diabetes torefer tothis proximity. In practice LADA isoften misdiagnosed
and as aconsequence not properly treated as type 2 diabetes.
The progression of -cell failure is slower than in common type 1 diabetes. Patients present more preserved cell function, the presence
at least one of four circulating autoantibodies topancreatic islet cell antigens and lack of requirement for insulin therapy at least 6 month
after diagnosis.
Patients with LADA have also lower BMI, fasting C peptide level, and lower insulin resistance (HOMA-IR) compared tothose with type2
diabetes.
Early insulin treatment in LADA leads tobetter preservation of metabolic control and toprotection of the -cell function.
Key words Type LADA diabetes, type 1 diabetes, type 2 diabetes, autoantibodies, diagnostics.
STRESZCZENIE. Cukrzyca typu LADA jest typem cukrzycy opodou autoimmunologicznym wystpujcym uosb dorosych. Zpunktu widzenia patogenezy posta tajest cilej zwizana zcukrzyc typu 1 wzwizku zczym niekiedy okrelana jest jako cukrzyca typu 1. Czsto
jest bdnie rozpoznawana anastpnie nieprawidowo leczona jako cukrzyca typu 2.
Przebieg procesu autoimmunologicznej destrukcji komrek trzustki jest wolniejszy ni wcukrzycy typu 1. Wmomencie rozpoznania LADA,
zachowana jest czciowa sekrecja komrek beta. Stwierdza si obecno przynajmniej 1 z4 autoprzeciwcia oraz nie wystpowanie koniecznoci leczenia insulin przez conajmniej 6miesicy odrozpoznania.
Pacjenci zcukrzyc typu LADA maj wchwili rozpoznania cukrzycy niszy wskanik BMI, nisze stenie peptydu C imniejsz insulinooporno
(HOMA-IR) wporwnaniu zpacjentami cukrzyc typu 2.
Wczesne leczenie insulin wcukrzycy typu LADA prowadzi dolepszej metabolicznej kontroli idoochrony funkcji komrek .
Sowa kluczowe Cukrzyca typu LADA, cukrzyca typu 1, cukrzyca typu 2, autoprzeciwciaa, diagnostyka.

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INTRODUCTION

DIAGNOSTIC REMARKS

The term LADA diabetes (Latent Autoimmune Diabetes in Adults) was introduced nearly 20 years ago. LADA
diabetes is aspecial form of type 1 diabetes, its beginning
takes place in adulthood. In contrast tothe classical type
1 diabetes, an autoimmune process of destruction of pancreatic islet cells is slower, hence the onset of the disease
occurs later. The age of 30 was previously indicated as the
beginning of the disease, but currently there is tendency
tomove it tothe limit of 25 years of age. Patients who are
diagnosed with this type of diabetes, in addition toolder
age, are characterized bythe lack of obesity, and usually
low levels of C-peptide. The presence of autoantibodies is
necessary for recognizing the LADA diabetes. In younger
patients these are mainly glutaminic acid decarboxylase
antibodies.
At present it is believed that the treatment of choice is
an early introduction of insulin aiming at slowing autoimmune cell damage.
Differentiation of diabetes types has along and still
unfinished story. It is reflected bythe history of the changes
in terminology as reminded below.
1. After the era of the perception of diabetes as ahomogeneous disease, at the beginning of XX century the division of diabetes was proposed in the following forms:
acute occurring in people under 40 years of age,
chronic in elderly people, often obese.
2. Then, other terms were also proposed:
insulin-sensitive diabetes,
insulin-insensitive diabetes.
Since 1964 the following distinction has started tobe
made:
juvenile diabetes mellitus,
adult-onset diabetes.
3. Subsequent years have seen the following terms:
IDDM: insulin-dependent diabetes mellitus resulting
from autoimmune destruction of cells, and
NIDDM: non-insulin dependent diabetes mellitus, resulting from acombination of insulin resistance and its
relative scarcity.
4. The progress of knowledge on diabetes etiology made
way for introducing of the actual terms (World Health
Organization, American Diabetes Association, European Association for the Study of Diabetes 1998).
type 1 diabetes, and
type 2 diabetes.
Successively other terms were added:
other specific types diabetes,
gestational diabetes mellitus.
The new classification and respective terminology is
actually expected.

The introduction of immunological and genetic tests

have broadened our understanding of the etiopathogenesis
of glucose metabolism disorders and requires arevision of
the currently existing classification of diabetes mellitus.
There is growing evidence that the current classification
obligatory since 1999 (1), in the light of current knowledge, requires verification.
In daily practice, when the type of diabetes diagnosis is based on clinical picture and very basic laboratory
examinations, it relatively often happens that erroneous
determination of the type of diabetes is made. According
toseveral authors, in many cases, after some time, one
should review the predetermined type of diabetes (2-6).
What are the basic, differential circumstances?
One of the elements underlying the differentiation of
types of diabetes is an interview and assessment of the
dynamics of symptoms development. Today, beyond any
doubt, weknow that this criterion is indeed in many cases
true, but quite often disappoints and its uncritical acceptance leads todiagnostic errors.
One of such examples is LADA type of diabetes, diagnosed as type 2 diabetes due tothe relatively slow progression of symptoms. It should be remembered that such
slowly developing type 1 diabetes with autoimmune basis
may also occur in juvenile patients. In this particular case
it is defined as LADY (Latent Autoimmune Diabetes in the
Young) or LADC (Latent Autoimmune Diabetes in Children) (7-11).
Another indicator taken into account for determining
the type of diabetes is the occurrence or non-occurrence of obesity. If hyperglycemia is found in apatient
with obesity or considerable degree of overweight it is
rather type 2 diabetes, but not always. In such cases,
one should check if it is not diabetes from the group
other types of diabetes, that is for example diabetes
accompanying genetic syndromes, endocrinopathies or
drug-induced diabetes.
Previously, age of the patient determined the classification of diabetes (juvenile diabetes mellitus or adult-onset diabetes). Although in children and adolescents the
most common is type 1 diabetes, in young age groups
may also be present all the different types of diabetes.
The errors may also result from diagnosing type 2 diabetes in all cases of diabetes in adult patients. It is known
that in these age groups monogenic diabetes and secondary diabetes, and increasingly recognized LADA diabetes
could be present. So if diabetes is diagnosed in patient aged
30-55 years, especially if it is anon-obese patient, account
should be taken torecognize monogenic diabetes or LADA
diabetes. Now this diagnostic age is being moved down
even tothe limit of 25 years. Proper and early diagnosis

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of LADA diabetes is very important because it is the base

for therapeutic decisions (12).
The Polish authors have recently published their findings on the prevalence of LADA diabetes (13). In their
research involving people aged 20-64 years, authors assessed the prevalence of LADA diabetes as 8.9% of newly
diagnosed diabetes.
In LADA the baseline level of C-peptide may be normal
or reduced, but the glucagon test lacks of physiological increase of its level, differently than it is in type 2
diabetes, wherein the level of C-peptide after glucagon
is increased, especially in the first years of disease (14).
Determining the presence of autoantibodies and tracking the dynamics of the rise of their titers is an important
element in the diagnosis of LADA diabetes (15,16).
The finding of high titers of autoantibodies against pancreatic islet structures, mainly Glutamic Acid Decarboxylase Antibodies (a/GAD) in patients aged 30-55 years, with
arelatively mild diabetes, makes the diagnosis of LADA
diabetes very likely (12,13,17-21).
According tosome authors autoantibodies titer is higher
in patients with afinal diagnosis of LADA diabetes than in
patients with type 1 diabetes. In older patients is often seen
an increase of tyrosine phosphatase-like protein antibodies
(IA2 antibodies) titer.
Some authors also note that ahigh titer of autoantibodies in LADA diabetes persists longer than in type 1 diabetes
(22). It probably is related tothe slower -cell destruction. The dynamics of insulin secretion is very important
in the diagnosis of diabetes LADA, as measured bythe
secretion after intravenous glucose load or as fasting and
post-glucagon C-peptide levels. In type LADA diabetes
insulin secretion is lower than in type 2 diabetes, although
at the onset of the disease it may be within the normal
range (23,24).
As one of the characteristics of LADA diabetes, an association of this type of diabetes with variability in genes
of the major histocompatibility HLA class II should be
considered (25).
Recently, more and more attention has been paid tothe
role of ZnT8 antibodies in the diagnosis of autoimmune
processes in diabetes. Zinc transporter 8 (ZnT8) has
been identified as anew autoantigen in patients with
diabetes. ZnT8 antibodies are considered tobe aspecific
marker of -cell damage. These antibodies appear later
than the anti-GAD, their occurrence is correlated with
the presence of anti-IA2 antibodies and they are considered tobe aparameter of tardily occurring humoral
response. Confirmation of their presence can facilitate
the differentiation of LADA diabetes from type 2 diabetes (26). It suggests also the risk of occurrence of autoimmune disorders associated with diabetes, including
autoimmune thyroid disease (26).

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In patients with LADA type diabetes one must remember about the possibility of the coexistence of other
autoimmune diseases, as it is in the classical type 1
diabetes (27-30).
Despite alot of research, many problems associated
with the pathogenesis of LADA diabetes are still tobe explained (18,31-34).

THERAPEUTIC REFLEXIONS
In many patients with LADA type diabetes, as aresult
of the initial diagnosis of type 2 diabetes, treatment is
initiated with sulfonylureas. Insulin treatment is usually
later prescribed. Currently, most of the authors present
the opinion that due tothe autoimmune nature, the insulin
therapy rather than sulfonylurea (SU) treatment is preferable toreverse or preserve -cell function among patients
with LADA. It is believed that the sulphonylureas can activate autoimmunity processes. Early insulin intervention
preserve -cell function and is indicated for patients with
type LADA diabetes (35,36). Depending on the dynamic
of autoimmunization processes, patients may temporarily adjust their glucose levels through diet and increased
physical activity, however, with the passing of the time
they require the inclusion of pharmacotherapy. Inclusion
of insulin should be made not later than 6 months after
diagnosis of diabetes, now it is increasingly considered that
this should take place already at the time of the diagnosis.
Insulin requirement is usually low for alonger period of
time, if patient make arecommended diet and physical
activity (37).
One may notice, that also exist suggestions for using
the immunomodulatory therapy with recombinant GAD65
inpatients with diabetes mellitus type LADA (12,38).

TOILLUSTRATE THE DIAGNOSTIC PROBLEMS,

THE DESCRIPTION OF SPECIFIC CASES
ISPRESENTED BELOW:
Case 1. 50-year-old patient, male with diabetes diagnosed when he was 37, treated with insulin mixture 30 units/day in two doses. The patient was very
poorly educated and practically did not regulate insulin
doses. The criteria et effective diabetes control were
never achieved. He was also treated for hypertension;
ophthalmological examination showed diabetic retinopathy. During the visit the casual glucose levels was
12.6mmol/l; HbA1c of 6.35%. BMI 22/kg/m2, waist
circumference of 90cm.
The whole picture suggested the diagnosis of LADA
diabetes. Completed studies have confirmed this diagnosis:
C-peptide was less than 0.1 ng/mL; titer of aGAD autoantibodies 99.93 IU/ml.

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The education was offered. Intensification of self-control, intensive insulin treatment with insulin analogues,
consultation of the nutritionist and increase of physical
activity were recommended.
Case 2. 37-year-old woman with diabetes diagnosed at
age of 35, insulin mixtures (30/70) in two doses were
steadily injected. The patient glucose levels were in the
range of 5 22mmol/l; the level of HbA1 was not determined. Due tohypothyroidism the patient has taken
Euthyrox for several years. Ahistory of huge obstetric
abnormalities 3 miscarriages, two births of children
with aweight greater than 4kg. The patient complained
on paresthesias and very extensive inflammation of the
oral mucosa. BMI 22.8kg/m2; waist circumference
79cm.
During the consultation in diabetological clinic fasting
blood glucose was 8.1mmol/l; HbA1c 8,4%; high titers
aGAD autoantibodies 1251.94 IU/ml; ATPO 197.3 IU/
ml; C-peptide level 0.1 ng/ml were found.
The whole picture permits the diagnosis of LADA
diabetes. The diabetes has probably existed many years
earlier. It was always poorly controlled. Consultation of
nutritionist, intensive self-control and intensive insulin
treatment with analogs were applied. The patient very
carefully began toimplement the recommendations and
the degree of metabolic control improved quickly.
Case 3. 42-year-old patient, male without obesity. Diagnosed with diabetes at the age of 39 (thirst, polyuria, blood glucose 22mmol/l; HbA1c of 9.3%). Insulin treatment was included early the daily dose was
between 24-28 units per day. Improvement of clinical
status was achieved.
After one year, insulin treatment had been discontinued,
metformin and sulphonylurea included, and after another
year pharmacotherapy was discontinued. In repeatedly
performed glycemia determinations following oral glucose load, glucose concentration remained at levels up
to14.7mmol/l 60 minutes after loading. The patient refused totake insulin applied only avery restrictive diet
and physical activity.
Later when LADA diabetes had been suspected, insulin
treatment was included. Self-control, and aconsultation of
nutritionist was recommended. The laboratory tests were
as follows:
C-peptide level of 0.69 ng/ml; the level of aGAD autoantibodies > 2000 IU/ml; ATPO 240.7 IU/ml, with normal levels of thyroid hormones.
These examinations confirmed the diagnosis of LADA
diabetes.
Case 4. 39-year-old male, diagnosed with diabetes
at the age of 38. Insulin mixture was included in two
chronic doses of 0,4 u/kg of body weight, blood glucose

concentration was determined only occasionally. One

year after being diagnosed with diabetes, the patient
had diabetological consultation. During the visit it was
found aslim physique (BMI 22.0kg/m2), very high
fasting blood glucose (22mmol/l), glycosuria without
acetonuria.
Intensive insulin treatment (0,7 u/kg of body weight/
day) was recommended. The education was offered.
Thelaboratory examinations were made HbA1c level
of 8.52%; C-peptide 0.69 ng/ml, ahigh titer of GAD antibodies 1183 IU/mL; thyroid hormones within the normal
range.
After two months, the improvement was obtained. The
treatment was maintained. The clinical picture indicates
the diagnosis of LADA diabetes.
Case 5. 37-year-old woman. BMI of 20,9kg/m2. At
34 years of age, during prophylactic tests diabetes was
found, blood glucose levels after an oral glucose load
were at time 0 6.7mmol/l; 120 min 16.7 mmol. Metformin was recommended.
After three years: fasting blood glucose above
11.1mmol/l; after meals up to22mmol/l. The patient was
referred todiabetological consultation.
Intensive self-control was instituted and intensive insulin therapy using analogues included. The consultation
of nutritionist was recommended, the education offered.
The laboratory examinations indicated the diagnosis of
LADA diabetes: C-peptide 0.98 ng/ml; GAD autoantibodies 437.5 IU/ml. Five months after the inclusion of insulin
HbA1c 7,1%; after 8 months HbA1c 6,66%; C-peptide
0,61 ng/ml; GAD autoantibodies 828,98 IU/ml.
Case 6. 36-year-old male. BMI of 22,5kg/m2. Diabetes
was diagnosed at 31 years of age, treated initially with
short acting insulin, then bysulfonylureas.
After 5 years since the diagnosis diabetes deterioration
of general condition occurred, patient was referred toconsult adiabetologist.
During the visit blood glucose 14.9mmol/l; HbA1c
10.5%.
LADA diabetes was suspected, intensive insulin treatment was applied. Intensive self-control and aconsultation
of nutritionist was recommended.
The laboratory examinations were made: C-peptide 1,86
ng/ml; a/GAD > 2000 IU/ml.
The consultation of ophthalmologist showed the presence of retinopathy.
The diagnosis of LADA diabetes was confirmed.
Case 7. 28-year-old woman with normal body weight
(BMI of 22,6kg/m2, waist circumference of 85cm).

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At 25 years of age, due tohyperglycemia found during

routine medical prophylactic examinations, type 2 diabetes
mellitus was diagnosed and metformin recommended.
After 3 years, due todeterioration of general condition,
the patient was referred toconsult diabetologist.
At the admission fasting blood glucose concentration
was found at the level of 13.9mmol/l; glucosuria and ketonuria were present; HbA1c of 11.31%;
On the basis of the clinical picture LADA diabetes was
suspected and intensive insulin treatment introduced.
The results of laboratory examinations confirmed the
diagnosis: C-peptide 1,82 ng/ml; a/GAD 103,07 IU/ml. In
the control after 7 months: HbA1c 7,2%; C-peptide 0,78
ng/ml; a/GAD 140 IU/ml.
Case 8. 37-year-old male, BMI of 22,8kg/m2. Because
of persistent inflammation of the urethra urine examination was made. Glucosuria was found, fasting blood
glucose concentration was increased up to12.8mmol/l.
The patient was referred toconsultant diabetologist.
During the visit: HbA1c 9,8%; BP 180/100 mmHg.
Suspecting LADA diabetes, intensive insulin treatment
was recommended. The results of laboratory examinations confirmed the diagnosis: C-peptide 0,44 ng/ml; a/
GAD 712IU/ml. After 7 months HbA1c level was 5,62%
Case 9. 32-year-old patient, BMI of 21,9kg/m2. Diabetes was recognized when the patient was 23 years
old. The patient controlled glycemia only occasionally,
insulin dosage was neglected, he was poorly educated.
Patient visited diabetologist in connection with the occurrence of hocks complaints. At the admission the
casual blood glucose level was 13.3mmol/l); HbA1C
7.58%; C-peptide 0.7 ng/ml; titer of aGAD autoantibodies 226.27 IU/ml. LADA type was diagnosed.
An intensive self-control, intensive insulin treatment
using analogues and consultation of nutritionist were recommended. Due tothe high level of CRP 70.56mg/l diagnostics towards arthritis was recommended.

DISCUSSION
In the group of 9 patients presented above, what attaches
attention is along period between the diagnosis of diabetes
and the time of proper diagnosis and therapy.
In 6 cases, it was aperiod of 1-5 years. In only one case,
the patient had diabetological consultation directly after
diagnosis of diabetes. In one case, this period was long
as 9 years and in another one even 13 years. It is interesting that the interview at the time of diagnosis of diabetes
and clinical picture could have suggested the diagnosis
of LADA diabetes even without performing immunological tests. Classical for LADA type age of diabetes
diagnosis, slim body, initially small insulin requirement,

38

indicated the necessity of more precise differentiation of

the type of diabetes (abnormal clinical course for the type
2 diabetes, secondary diabetes, MODY diabetes). Very
disturbing is the fact that patients were young, professionally active, having afamily, their life expectancy extended
for many years. None of these patients was educated for
the proper controlling of diabetes, insulin dose adjustment
skills, proper nutrition.
Most of these patients did not present very marked
HbA1c level. None of the patients was tested for C-peptide
levels or titers of antipancreatic autoantibodies. None of
patients had regular self-control. The awareness of hypoglycemia was very low, none of the patients had GlucaGen.
The patients were not well trained in the rules governing
the management of motor vehicles.
Some doubts may raise the diagnosis of the type of
diabetes in the case no. 9. One can discuss whether it is
LADA diabetes or classical type 1 diabetes. Borderline
patient age at diagnosis may suggest the diagnosis of type
1, although the relatively slow increase in insulin requirements, and absence of ketosis seems tospeak rather for the
diagnosis of LADA type. Of course one could take early
enough amore accurate diagnostic tests, but from the point
of view of the patient such differentiation did not matter.
Both cases required intensive insulin therapy.
Presented cases confirmed the necessity of careful observation of patients in afew years after diagnosis of diabetes, regardless of what type of diabetes had been diagnosed
at the time of the disease onset.
Analysis of cases classified as LADA type confirms the
need for careful analysis of the pathogenic traits of glucose
homeostasis in patients in the age group ranging from 25
to55 years, especially in those without concomitant obesity and without family history of diabetes.
Critical for differentiation is the determination of the
titers of autoantibodies. Also determination of C-peptide
levels is strongly recommended for confirmatory diagnosis
of LADA.
Early diagnosis of LADA diabetes, and early application
of insulin therapy are very important for the prevention of
chronic complications and slowing down of the autoimmune destruction of beta cells. Very unfavorable in these
patients is the using of sulphonylureas this is unfortunately, often the result of misdiagnosis.

REFERENCES
1. Word Health Organization: Definition, diagnosis and
classification of diabetes mellitus and its complications. Report of aWHO Consultation. Geneva 1999.
2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33
Suppl 1:S62-69.

Medycyna Metaboliczna, 2015, tom XIX, nr 4

www.medycyna-metaboliczna.pl

3. Maecki M., Skupie J. Problems in differential diagnosis of diabetes types. Pol Arch Med Wewn.
2008;118:435-440.
4. Otto-Buczkowska E., Jarosz-Chobot P., Machnica L.
Diabetes mellitus type 1, type 2 or type 1.5 dilemmas in making proper diagnosis. DDK/ECD 2008;
8:91-94.
5. Thethy I, Robertson L, Swaminathan K. Diagnosis in
diabetes: does it matter? J R Coll Physicians Edinb.
2011;41:119-121.
6. Ziegler AG, Meier-Stiegen F, Winkler C, Bonifacio E;
the TEENDIAB Study Group. Prospective evaluation
of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty TEENDIAB:
study design. Pediatr Diabetes. 2012;13:438-443.
7. Aycan Z, Berberoglu M, Adiyaman P, iwsp.: Latent
autoimmune diabetes mellitus in children (LADC)
with autoimmune thyroiditis and celiac disease. J
Pediatr Endocrinol Metab. 2004 Nov; 17 (11): 1565-9.
8. Bering B, Devendra D. Latent autoimmune diabetes in
the young. Clin Med. 2009;9:93; author reply 93-94.
9. Otto-Buczkowska E. (Type LADA diabetes--interrogation points). Przegl Lek 2013; 70: 25-27.
10. Zachariah S, Sharfi MO, Nussey SS, Bano G.Latent
autoimmune diabetes in the young. Clin Med.
2008;8:552-553.
11. Thunander M, Thorgeirsson H, Trn C, iwsp.: -cell
function and metabolic control in latent autoimmune
diabetes in adults with early insulin versus conventional treatment: a3-year follow-up. Eur J Endocrinol.
2011;164:239-245.
12. Szepietowska B, Gbocka A, Puch U, iwsp.: Latent
autoimmune diabetes in adults in apopulation-based
cohort of Polish patients with newly diagnosed diabetes mellitus. Arch Med Sci. 2012;8:491-495.
13. Chaillous L, Bouhanick B, Kerlan V, iwsp.: Clinical
and metabolic characteristics of patients with latent
autoimmune diabetes in adults (LADA): absence of
rapid beta-cell loss in patients with tight metabolic
control. Diabetes Metab. 2010;36:64-70.
14. Srgjerd EP, Skorpen F, Kvaly K, iwsp.: Prevalence of ZnT8 antibody in relation tophenotype and
SLC30A8 polymorphism in adult autoimmune diabetes: results from the HUNT study, Norway. Autoimmunity. 2013;46:74-79.
15. Zhou Z, Xiang Y, Ji L, iwsp.: LADA China Study
Group. Collaborators (45) Frequency, immunogenetics, and clinical characteristics of latent autoimmune
diabetes in China (LADA China study): anationwide,
multicenter, clinic-based cross-sectional study. Diabetes. 2013;62:543-550.
16. Brophy S, Davies H, Dunseath G, iwsp.: Experience
of the introduction of routine antibody testing in primary care and of running atrial for latent autoimmune

diabetes in adults (LADA). Diabetes Res Clin Pract.

2011;93:e49-52.
17. Brophy S, Davies H, Mannan S, iwsp.: Interventions
for latent autoimmune diabetes (LADA) in adults.
Cochrane Database Syst Rev. 2011; (9): CD006165.
18. Hawa MI, Kolb H, Schloot N, iwsp.: Action LADA
consortium. Adult-onset autoimmune diabetes in Europe is prevalent with abroad clinical phenotype: Action LADA 7. Diabetes Care. 2013;36:908-913. Erratum in: Diabetes Care. 2014;37:1494.
19. Hillman M, Trn C, Landin-Olsson M; DISS study
group. The glutamic acid decarboxylase 65 immunoglobulin G subclass profile differs between adult-onset type 1 diabetes and latent autoimmune diabetes in
adults (LADA) up to3 years after clinical onset. Clin
Exp Immunol. 2009;157:255-260.
20. Weber P, Ambrosova P, Canov P, iwsp.: GAD antibodies in T1D and LADA--relations toage, BMI,
c-peptide, IA-2 and HLA-DRB1*03 and DRB1*04
alleles. Adv Gerontol. 2011;24:312-318.
21. Djekic K, Mouzeyan A, Ipp E. Latent autoimmune
diabetes of adults is phenotypically similar totype 1
diabetesin aminority population. J Clin Endocrinol
Metab. 2012;97:E409-413.
22. Lee SH, Kwon HS, Yoo SJ, iwsp.: Identifying latent
autoimmune diabetes in adults in Korea: the role of
C-peptide and metabolic syndrome. Diabetes Res Clin
Pract. 2009;83:e62-65.
23. Srgjerd EP, Skorpen F, Kvaly K, iwsp.: Time dynamics of autoantibodies are coupled tophenotypes
and add tothe heterogeneity of autoimmune diabetes
in adults: the HUNT study, Norway. Diabetologia.
2012;55:1310-1318.
24. Pettersen E, Skorpen F, Kvaly K., iwsp.: Genetic
heterogeneity in latent autoimmune diabetes is linked
tovarious degrees of autoimmune activity: results
from the Nord-Trndelag Health Study. Diabetes.
2010;59:302-310.
25. Huang G, Xiang Y, Pan L, iwsp.: Zinc transporter 8
autoantibody (ZnT8A) could help differentiate latent
autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetes mellitus. Diabetes Metab Res
Rev. 2013;29:363-368.
26. Rogowicz-Frontczak A1, Zozuliska-Zikiewicz
D, Litwinowicz M, iwsp.: Are zinc transporter type
8 antibodies amarker of autoimmune thyroiditis in
non-obese adults with new-onset diabetes? Eur J Endocrinol. 2014;170:651-658.
27. Jin P, Huang G, Lin J, iwsp.: Epitope analysis of
GAD65 autoantibodies in adult-onset type 1 diabetes
and latent autoimmune diabetes in adults with thyroid
autoimmunity. Acta Diabetol. 2011;48:149-155.
28. Jin P, Huang G, Lin J, iwsp.: High titre of antiglutamic acid decarboxylase autoantibody is astrong

Medycyna Metaboliczna, 2015, tom XIX, nr 4

www.medycyna-metaboliczna.pl

39

predictor of the development of thyroid autoimmunity in patients with type 1 diabetes and latent autoimmune diabetes in adults. Clin Endocrinol (Oxf).
2011;74:587-592.
29. Otto-Buczkowska E., Deja G. (Polygladular autoimmune syndromes.) Physican 2008; 12:44-52.
30. Zampetti S, Capizzi M, Spoletini M, iwsp.: NIRAD
Study Group. GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according togender (NIRAD study 6). J Clin Endocrinol
Metab. 2012;97:3759-3765.
31. Andersen MK, Lundgren V, Turunen JA, iwsp.: Latent autoimmune diabetes in adults differs genetically
from classical type 1 diabetes diagnosed after the age
of 35 years. Diabetes Care. 2010;33:2062-2064.
32. Jin P, Huang G, Lin J., iwsp.: Epitope analysis of
GAD65 autoantibodies in adult-onset type 1 diabetes
and latent autoimmune diabetes in adults with thyroid
autoimmunity. Acta Diabetol. 2011;48:149-155.
33. Nambam B, Aggarwal S, Jain A. Latent autoimmune
diabetes in adults: Adistinct but heterogeneous clinical entity. World J Diabetes. 2010;1:111-115.
34. Szepietowska B, Moczulski D, Wawrusiewicz-Kurylonek N, iwsp.: Transcription factor 7-like 2-gene

polymorphism is related tofasting C peptide in latent

autoimmune diabetes in adults (LADA). Acta Diabetol. 2010;47:83-86.
35. Poudel RR. Latent autoimmune diabetes of adults:
From oral hypoglycemic agents toearly insulin. Indian J Endocrinol Metab. 2012;16 Suppl 1:S41-6.
36. Rosrio PW, Reis JS, Fagundes TA, iwsp.: Latent
autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of
early insulinization. Arq Bras Endocrinol Metabol.
2007;51:52-58.
37. Jachimowicz-Duda O., Zorena K., Myliwiec M. Zastosowanie maych dawek insuliny dugodziaajcej
jako skutecznej terapii wcukrzycy typu LADA opisy
przypadkw. Diabetol. Klin. 2014;3:79-83,
38. Ludvigsson J. Therapy with GAD in diabetes. Diabetes Metab Res Rev. 2009;25: 307-315.
Corresponding author:
Professor Ewa Otto-Buczkowska MD, PhD
Jasnogrska 26/21, 44-100 Gliwice Poland
e-mail: em.buczkowski@pro.onet.pl

INERTIA MEDICA
Ulepszanie opieki medycznej ispoecznej nad 3-milionow subpopulacj chorych nacukrzyc wPolsce stao si
napocztku XXI wieku jednym zpriorytetw systemu ochrony zdrowia. Wiele osb iinstytucji odpowiedzialnych
zaksztatowanie opieki diabetologicznej nie jest wstanie wystarczajco jasno sobie touwiadomi. Tacierpka
uwaga dotyczy wielu przedstawicieli wadz, lekarzy iinnych osb zkrgu opieki medycznej ispoeczestwa.
Nietrudno udowodni, zeskutkiem tego stanu rzeczy sdue straty ludzkie iekonomiczne.
Towarzystwo Edukacji Terapeutycznej (Warszawa) postuluje wprowadzenie systemowej kontroli jakoci leczenia
cukrzycy wewszystkich orodkach opieki diabetologicznej co1 rok. Orodki oniskiej jakoci leczenia powinny by
poddane dodatkowej edukacji.

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Medycyna Metaboliczna, 2015, tom XIX, nr 4

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